Hedgehog transcriptional effector GLI mediates mTOR-Induced PD-L1 expression in gastric cancer organoids
Tumors evade immune surveillance by expressing Programmed Death-Ligand 1 (PD-L1), subsequently inhibiting CD8+ cytotoxic T lymphocyte function. Response of gastric cancer to immunotherapy is relatively low. Our laboratory has reported that Helicobacter pylori-induced PD-L1 expression within the gast...
Saved in:
| Published in | Cancer letters Vol. 518; pp. 59 - 71 |
|---|---|
| Main Authors | , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Ireland
Elsevier B.V
10.10.2021
Elsevier Limited |
| Subjects | |
| Online Access | Get full text |
Cover
Loading…
| Abstract | Tumors evade immune surveillance by expressing Programmed Death-Ligand 1 (PD-L1), subsequently inhibiting CD8+ cytotoxic T lymphocyte function. Response of gastric cancer to immunotherapy is relatively low. Our laboratory has reported that Helicobacter pylori-induced PD-L1 expression within the gastric epithelium is mediated by the Hedgehog (Hh) signaling pathway. The PI3K/AKT/mTOR pathway is activated in gastric cancer and may have immunomodulatory potential. We hypothesize that Hh signaling mediates mTOR-induced PD-L1 expression. Patient-derived organoids (PDOs) were generated from gastric biopsies and resected tumor tissues. Autologous organoid/immune cell co-cultures were used to study the immunosuppressive function of MDSCs. NanoString Digital Spatial Profiling (DSP) of immune-related protein markers using FFPE slide-mounted tissues from gastric cancer patients was performed. DSP analysis showed infiltration of immunosuppressive MDSCs expressing Arg1, CD66b, VISTA and IDO1 within cancer tissues. Orthotopic transplantation of patient derived organoids (PDOs) resulted in the engraftment of organoids and the development of histology similar to that observed in the patient's tumor tissue. PDO/immune cell co-cultures revealed that PD-L1-expressing organoids were unresponsive to nivolumab in vitro in the presence of PMN-MDSCs. Depletion of PMN-MDSCs within these co-cultures sensitized the organoids to anti-PD-1/PD-L1-induced cancer cell death. Rapamycin decreased phosphorylated S6K, Gli2 and PD-L1 expression in PDO/immune cell co-cultures. Transcriptional regulation of PD-L1 by GLI1 and GLI2 was blocked by rapamycin. In conclusion, the PDO/immune cell co-cultures may be used to study immunosuppressive MDSC function within the gastric tumor microenvironment. The mTOR signaling pathway mediates GLI-induced PD-L1 expression in gastric cancer.
•Myeloid derived suppressor cells (MDSCs) accumulate within the tumor microenvironment (TME) and may contribute to resistance to immunotherapy.•The PI3K/AKT/mTOR pathway is activated in gastric cancer and may have immunomodulatory potential.•An autologous cancer PDO/immune cell co-culture system may be used to investigate PD-L1/PD-1 blockade together with the inhibition of immunosuppressive cells MDSCs.•The mTOR pathway mediates the non-canonical Hedgehog signaling cascade to induce PD-L1 expression.•The mTOR signaling pathway may be targeted to decrease PD-L1 expression and increase response to immunotherapy in gastric cancer. |
|---|---|
| AbstractList | Tumors evade immune surveillance by expressing Programmed Death-Ligand 1 (PD-L1), subsequently inhibiting CD8+ cytotoxic T lymphocyte function. Response of gastric cancer to immunotherapy is relatively low. Our laboratory has reported that Helicobacter pylori-induced PD-L1 expression within the gastric epithelium is mediated by the Hedgehog (Hh) signaling pathway. The PI3K/AKT/mTOR pathway is activated in gastric cancer and may have immunomodulatory potential. We hypothesize that Hh signaling mediates mTOR-induced PD-L1 expression. Patient-derived organoids (PDOs) were generated from gastric biopsies and resected tumor tissues. Autologous organoid/immune cell co-cultures were used to study the immunosuppressive function of MDSCs. NanoString Digital Spatial Profiling (DSP) of immune-related protein markers using FFPE slide-mounted tissues from gastric cancer patients was performed. DSP analysis showed infiltration of immunosuppressive MDSCs expressing Arg1, CD66b, VISTA and IDO1 within cancer tissues. Orthotopic transplantation of patient derived organoids (PDOs) resulted in the engraftment of organoids and the development of histology similar to that observed in the patient's tumor tissue. PDO/immune cell co-cultures revealed that PD-L1-expressing organoids were unresponsive to nivolumab in vitro in the presence of PMN-MDSCs. Depletion of PMN-MDSCs within these co-cultures sensitized the organoids to anti-PD-1/PD-L1-induced cancer cell death. Rapamycin decreased phosphorylated S6K, Gli2 and PD-L1 expression in PDO/immune cell co-cultures. Transcriptional regulation of PD-L1 by GLI1 and GLI2 was blocked by rapamycin. In conclusion, the PDO/immune cell co-cultures may be used to study immunosuppressive MDSC function within the gastric tumor microenvironment. The mTOR signaling pathway mediates GLI-induced PD-L1 expression in gastric cancer.
•Myeloid derived suppressor cells (MDSCs) accumulate within the tumor microenvironment (TME) and may contribute to resistance to immunotherapy.•The PI3K/AKT/mTOR pathway is activated in gastric cancer and may have immunomodulatory potential.•An autologous cancer PDO/immune cell co-culture system may be used to investigate PD-L1/PD-1 blockade together with the inhibition of immunosuppressive cells MDSCs.•The mTOR pathway mediates the non-canonical Hedgehog signaling cascade to induce PD-L1 expression.•The mTOR signaling pathway may be targeted to decrease PD-L1 expression and increase response to immunotherapy in gastric cancer. Tumors evade immune surveillance by expressing Programmed Death-Ligand 1 (PD-L1), subsequently inhibiting CD8 cytotoxic T lymphocyte function. Response of gastric cancer to immunotherapy is relatively low. Our laboratory has reported that Helicobacter pylori-induced PD-L1 expression within the gastric epithelium is mediated by the Hedgehog (Hh) signaling pathway. The PI3K/AKT/mTOR pathway is activated in gastric cancer and may have immunomodulatory potential. We hypothesize that Hh signaling mediates mTOR-induced PD-L1 expression. Patient-derived organoids (PDOs) were generated from gastric biopsies and resected tumor tissues. Autologous organoid/immune cell co-cultures were used to study the immunosuppressive function of MDSCs. NanoString Digital Spatial Profiling (DSP) of immune-related protein markers using FFPE slide-mounted tissues from gastric cancer patients was performed. DSP analysis showed infiltration of immunosuppressive MDSCs expressing Arg1, CD66b, VISTA and IDO1 within cancer tissues. Orthotopic transplantation of patient derived organoids (PDOs) resulted in the engraftment of organoids and the development of histology similar to that observed in the patient's tumor tissue. PDO/immune cell co-cultures revealed that PD-L1-expressing organoids were unresponsive to nivolumab in vitro in the presence of PMN-MDSCs. Depletion of PMN-MDSCs within these co-cultures sensitized the organoids to anti-PD-1/PD-L1-induced cancer cell death. Rapamycin decreased phosphorylated S6K, Gli2 and PD-L1 expression in PDO/immune cell co-cultures. Transcriptional regulation of PD-L1 by GLI1 and GLI2 was blocked by rapamycin. In conclusion, the PDO/immune cell co-cultures may be used to study immunosuppressive MDSC function within the gastric tumor microenvironment. The mTOR signaling pathway mediates GLI-induced PD-L1 expression in gastric cancer. Tumors evade immune surveillance by expressing Programmed Death-Ligand 1 (PD-L1), subsequently inhibiting CD8+ cytotoxic T lymphocyte function. Response of gastric cancer to immunotherapy is relatively low. Our laboratory has reported that Helicobacter pylori-induced PD-L1 expression within the gastric epithelium is mediated by the Hedgehog (Hh) signaling pathway. The PI3K/AKT/mTOR pathway is activated in gastric cancer and may have immunomodulatory potential. We hypothesize that Hh signaling mediates mTOR-induced PD-L1 expression. Patient-derived organoids (PDOs) were generated from gastric biopsies and resected tumor tissues. Autologous organoid/immune cell co-cultures were used to study the immunosuppressive function of MDSCs. NanoString Digital Spatial Profiling (DSP) of immune-related protein markers using FFPE slide-mounted tissues from gastric cancer patients was performed. DSP analysis showed infiltration of immunosuppressive MDSCs expressing Arg1, CD66b, VISTA and IDO1 within cancer tissues. Orthotopic transplantation of patient derived organoids (PDOs) resulted in the engraftment of organoids and the development of histology similar to that observed in the patient's tumor tissue. PDO/immune cell co-cultures revealed that PD-L1-expressing organoids were unresponsive to nivolumab in vitro in the presence of PMN-MDSCs. Depletion of PMN-MDSCs within these co-cultures sensitized the organoids to anti-PD-1/PD-L1-induced cancer cell death. Rapamycin decreased phosphorylated S6K, Gli2 and PD-L1 expression in PDO/immune cell co-cultures. Transcriptional regulation of PD-L1 by GLI1 and GLI2 was blocked by rapamycin. In conclusion, the PDO/immune cell co-cultures may be used to study immunosuppressive MDSC function within the gastric tumor microenvironment. The mTOR signaling pathway mediates GLI-induced PD-L1 expression in gastric cancer. Tumors evade immune surveillance by expressing Programmed Death-Ligand 1 (PD-L1), subsequently inhibiting CD8+ cytotoxic T lymphocyte function. Response of gastric cancer to immunotherapy is relatively low. Our laboratory has reported that Helicobacter pylori-induced PD-L1 expression within the gastric epithelium is mediated by the Hedgehog (Hh) signaling pathway. The PI3K/AKT/mTOR pathway is activated in gastric cancer and may have immunomodulatory potential. We hypothesize that Hh signaling mediates mTOR-induced PD-L1 expression. Patient-derived organoids (PDOs) were generated from gastric biopsies and resected tumor tissues. Autologous organoid/immune cell co-cultures were used to study the immunosuppressive function of MDSCs. NanoString Digital Spatial Profiling (DSP) of immune-related protein markers using FFPE slide-mounted tissues from gastric cancer patients was performed. DSP analysis showed infiltration of immunosuppressive MDSCs expressing Arg1, CD66b, VISTA and IDO1 within cancer tissues. Orthotopic transplantation of patient derived organoids (PDOs) resulted in the engraftment of organoids and the development of histology similar to that observed in the patient's tumor tissue. PDO/immune cell co-cultures revealed that PD-L1-expressing organoids were unresponsive to nivolumab in vitro in the presence of PMN-MDSCs. Depletion of PMN-MDSCs within these co-cultures sensitized the organoids to anti-PD-1/PD-L1-induced cancer cell death. Rapamycin decreased phosphorylated S6K, Gli2 and PD-L1 expression in PDO/immune cell co-cultures. Transcriptional regulation of PD-L1 by GLI1 and GLI2 was blocked by rapamycin. In conclusion, the PDO/immune cell co-cultures may be used to study immunosuppressive MDSC function within the gastric tumor microenvironment. The mTOR signaling pathway mediates GLI-induced PD-L1 expression in gastric cancer.Tumors evade immune surveillance by expressing Programmed Death-Ligand 1 (PD-L1), subsequently inhibiting CD8+ cytotoxic T lymphocyte function. Response of gastric cancer to immunotherapy is relatively low. Our laboratory has reported that Helicobacter pylori-induced PD-L1 expression within the gastric epithelium is mediated by the Hedgehog (Hh) signaling pathway. The PI3K/AKT/mTOR pathway is activated in gastric cancer and may have immunomodulatory potential. We hypothesize that Hh signaling mediates mTOR-induced PD-L1 expression. Patient-derived organoids (PDOs) were generated from gastric biopsies and resected tumor tissues. Autologous organoid/immune cell co-cultures were used to study the immunosuppressive function of MDSCs. NanoString Digital Spatial Profiling (DSP) of immune-related protein markers using FFPE slide-mounted tissues from gastric cancer patients was performed. DSP analysis showed infiltration of immunosuppressive MDSCs expressing Arg1, CD66b, VISTA and IDO1 within cancer tissues. Orthotopic transplantation of patient derived organoids (PDOs) resulted in the engraftment of organoids and the development of histology similar to that observed in the patient's tumor tissue. PDO/immune cell co-cultures revealed that PD-L1-expressing organoids were unresponsive to nivolumab in vitro in the presence of PMN-MDSCs. Depletion of PMN-MDSCs within these co-cultures sensitized the organoids to anti-PD-1/PD-L1-induced cancer cell death. Rapamycin decreased phosphorylated S6K, Gli2 and PD-L1 expression in PDO/immune cell co-cultures. Transcriptional regulation of PD-L1 by GLI1 and GLI2 was blocked by rapamycin. In conclusion, the PDO/immune cell co-cultures may be used to study immunosuppressive MDSC function within the gastric tumor microenvironment. The mTOR signaling pathway mediates GLI-induced PD-L1 expression in gastric cancer. |
| Author | Torvund, Meaghan Helmrath, Michael A. Koh, Vivien Shabbir, Asim Hawkins, Jennifer A. Ito, Yoshiaki Ahmed, Syed A. Yong, Wei Peng Zavros, Yana Steele, Nina Yan So, Jimmy Bok Chakrabarti, Jayati Wang, Jiang Merchant, Juanita L. |
| AuthorAffiliation | 1 National University Cancer Institute Singapore, National University Health System, Singapore 2 Cancer Science Institute of Singapore, National University of Singapore 3 Department of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ, USA 5 Department of Pediatric Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA 10 Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore 9 Department of Surgery, National University Hospital, Singapore 7 Department of Gastroenterology and Hepatology, University of Arizona College of Medicine, Tucson AZ, USA 4 Department of Cell and Developmental Biology and Department of Surgery, University of Michigan, Ann Arbor MI, USA 6 Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA 8 Department of Surgery, University of Cincinnati Cancer Institute, Cincinnati, OH, USA |
| AuthorAffiliation_xml | – name: 8 Department of Surgery, University of Cincinnati Cancer Institute, Cincinnati, OH, USA – name: 2 Cancer Science Institute of Singapore, National University of Singapore – name: 1 National University Cancer Institute Singapore, National University Health System, Singapore – name: 5 Department of Pediatric Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA – name: 7 Department of Gastroenterology and Hepatology, University of Arizona College of Medicine, Tucson AZ, USA – name: 9 Department of Surgery, National University Hospital, Singapore – name: 3 Department of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ, USA – name: 6 Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA – name: 4 Department of Cell and Developmental Biology and Department of Surgery, University of Michigan, Ann Arbor MI, USA – name: 10 Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore |
| Author_xml | – sequence: 1 givenname: Vivien surname: Koh fullname: Koh, Vivien organization: National University Cancer Institute Singapore, National University Health System, Singapore – sequence: 2 givenname: Jayati orcidid: 0000-0003-2265-4657 surname: Chakrabarti fullname: Chakrabarti, Jayati organization: Department of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ, USA – sequence: 3 givenname: Meaghan orcidid: 0000-0002-8997-5909 surname: Torvund fullname: Torvund, Meaghan organization: Department of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ, USA – sequence: 4 givenname: Nina surname: Steele fullname: Steele, Nina organization: Department of Cell and Developmental Biology and Department of Surgery, University of Michigan, Ann Arbor, MI, USA – sequence: 5 givenname: Jennifer A. surname: Hawkins fullname: Hawkins, Jennifer A. organization: Department of Pediatric Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA – sequence: 6 givenname: Yoshiaki surname: Ito fullname: Ito, Yoshiaki organization: Cancer Science Institute of Singapore, National University of Singapore, Singapore – sequence: 7 givenname: Jiang surname: Wang fullname: Wang, Jiang organization: Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA – sequence: 8 givenname: Michael A. surname: Helmrath fullname: Helmrath, Michael A. organization: Department of Pediatric Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA – sequence: 9 givenname: Juanita L. orcidid: 0000-0002-6559-8184 surname: Merchant fullname: Merchant, Juanita L. organization: Department of Gastroenterology and Hepatology, University of Arizona College of Medicine, Tucson, AZ, USA – sequence: 10 givenname: Syed A. surname: Ahmed fullname: Ahmed, Syed A. organization: Department of Surgery, University of Cincinnati Cancer Institute, Cincinnati, OH, USA – sequence: 11 givenname: Asim orcidid: 0000-0002-2490-6478 surname: Shabbir fullname: Shabbir, Asim organization: Department of Surgery, National University Hospital, Singapore – sequence: 12 givenname: Jimmy Bok surname: Yan So fullname: Yan So, Jimmy Bok organization: National University Cancer Institute Singapore, National University Health System, Singapore – sequence: 13 givenname: Wei Peng surname: Yong fullname: Yong, Wei Peng organization: National University Cancer Institute Singapore, National University Health System, Singapore – sequence: 14 givenname: Yana orcidid: 0000-0002-1266-6470 surname: Zavros fullname: Zavros, Yana email: yzavros@email.arizona.edu organization: Department of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ, USA |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/34126195$$D View this record in MEDLINE/PubMed |
| BookMark | eNqFkVGLEzEUhYOsuN3qPxAJ-OLL1GSSycyICLLq7kJhRdbnkLm506ZOk24yXdx_b0rron0pBO5Dzjmce78LcuaDR0JeczbjjKv3qxkYP-A4K1nJZ0zNGKufkQlv6rKo24adkQkTTBaiEdU5uUhpxRirZF29IOdC8lLxtpqQ5TXaBS7Dgo7R-ATRbUYXvBko9j3CGCK9mt_QNVpnRkx0fXf7o7jxdgto6fcvxZxT_L2JmFJ2UefpwqQxOqC5HGCkIS6MD86ml-R5b4aErw5zSn5--3p3eV3Mb69uLj_PC6ikHAvLZC1lbRDa0nY9E02rGgFN10oEhR0TfS8ryQA6VYMUyvStFAgWlK062Ysp-bTP3Wy73BrQ58UGvYlubeKjDsbp_3-8W-pFeNCNYkrkNyXvDgEx3G8xjXrtEuAwGI9hm3RZSS5KLpsyS98eSVdhG_PxdqqqYY3IN86qN_82eqryF0IWyL0AYkgpYv8k4UzvWOuV3rPWO9aaKZ1ZZ9uHIxu40ezo5b3ccMp8OBNmFg8Oo07gMCOzLmbs2gZ3KuDjUQAMzjswwy98PG3_A8FS3OE |
| CitedBy_id | crossref_primary_10_1016_j_biopha_2023_115514 crossref_primary_10_1016_j_trecan_2024_03_008 crossref_primary_10_3389_fonc_2023_1171418 crossref_primary_10_1002_cai2_101 crossref_primary_10_3389_pore_2023_1610893 crossref_primary_10_1016_j_cellsig_2023_110998 crossref_primary_10_3389_fgene_2023_1238248 crossref_primary_10_3390_cancers13246158 crossref_primary_10_1016_j_apsb_2025_03_026 crossref_primary_10_1186_s13045_024_01654_2 crossref_primary_10_2147_IJN_S424737 crossref_primary_10_1002_cam4_4456 crossref_primary_10_1016_j_canlet_2025_217589 crossref_primary_10_1088_1758_5090_ad3e30 crossref_primary_10_1186_s40364_022_00421_0 crossref_primary_10_3390_biom13050875 crossref_primary_10_1038_s41392_022_01190_w crossref_primary_10_12677_acm_2024_1482255 crossref_primary_10_1136_jitc_2022_006290 crossref_primary_10_3390_cells13201726 crossref_primary_10_3390_ijms24108862 crossref_primary_10_1016_j_gendis_2023_02_052 crossref_primary_10_3390_ijms252111735 crossref_primary_10_1016_j_phymed_2022_154227 crossref_primary_10_1038_s41392_023_01559_5 crossref_primary_10_1186_s12943_023_01867_y crossref_primary_10_1186_s13045_022_01242_2 crossref_primary_10_3390_cimb46020081 crossref_primary_10_1186_s12953_024_00231_2 crossref_primary_10_1007_s42242_022_00206_2 crossref_primary_10_3389_fimmu_2022_1060497 crossref_primary_10_3389_fimmu_2022_923477 crossref_primary_10_1016_j_actbio_2022_04_050 crossref_primary_10_1016_j_jep_2024_118081 crossref_primary_10_3390_ijms241915016 crossref_primary_10_3892_or_2024_8775 crossref_primary_10_1016_j_canlet_2024_216992 crossref_primary_10_7555_JBR_35_20210091 crossref_primary_10_1038_s41419_023_06358_y crossref_primary_10_1063_5_0216185 crossref_primary_10_1186_s40364_024_00577_x crossref_primary_10_1038_s41571_023_00767_w crossref_primary_10_1016_j_jbo_2024_100625 crossref_primary_10_3389_fphar_2023_1159829 crossref_primary_10_7717_peerj_17860 crossref_primary_10_1155_2023_2021515 crossref_primary_10_4251_wjgo_v16_i5_1725 crossref_primary_10_1038_s41416_022_01839_x crossref_primary_10_1093_jnci_djac085 crossref_primary_10_1002_mco2_437 crossref_primary_10_1016_j_mam_2025_101358 crossref_primary_10_18632_aging_205132 crossref_primary_10_1038_s41392_022_01194_6 crossref_primary_10_1016_j_mtbio_2022_100502 crossref_primary_10_1016_j_intimp_2024_113892 crossref_primary_10_18632_aging_204817 crossref_primary_10_5306_wjco_v16_i4_102397 crossref_primary_10_1111_hel_12999 crossref_primary_10_1016_j_semcancer_2021_12_004 crossref_primary_10_1016_j_xcrm_2024_101777 crossref_primary_10_1177_10732748221134398 crossref_primary_10_3390_biom12101503 crossref_primary_10_3389_fonc_2021_762184 crossref_primary_10_1002_ctm2_1802 crossref_primary_10_3390_biomedicines9091188 crossref_primary_10_1038_s41419_025_07564_6 crossref_primary_10_11569_wcjd_v31_i10_389 crossref_primary_10_1186_s12964_024_01812_6 crossref_primary_10_1002_advs_202310037 crossref_primary_10_1016_j_biopha_2023_114338 crossref_primary_10_1186_s13046_024_03034_7 crossref_primary_10_1186_s13046_023_02653_w crossref_primary_10_1002_mco2_535 crossref_primary_10_3389_fonc_2022_862462 crossref_primary_10_1016_j_canlet_2023_216180 crossref_primary_10_1016_j_pharmthera_2022_108276 crossref_primary_10_1002_adhm_202400475 crossref_primary_10_1146_annurev_cancerbio_061421_040659 crossref_primary_10_1007_s00253_022_12011_z crossref_primary_10_3390_ijms25031848 crossref_primary_10_3390_organoids2030011 crossref_primary_10_1002_adhm_202401843 crossref_primary_10_1016_j_biopha_2023_114601 crossref_primary_10_1371_journal_pgen_1010629 crossref_primary_10_3390_cells12071001 crossref_primary_10_1016_j_heliyon_2024_e32965 crossref_primary_10_32604_or_2023_029494 crossref_primary_10_2174_1568009623666221027101637 crossref_primary_10_1016_j_canlet_2023_216351 crossref_primary_10_3390_cells12081165 crossref_primary_10_1002_advs_202302640 crossref_primary_10_1186_s13045_022_01278_4 crossref_primary_10_1002_cbic_202400731 crossref_primary_10_1016_j_canlet_2024_217106 crossref_primary_10_3892_ijo_2024_5629 crossref_primary_10_1186_s12943_024_02084_x crossref_primary_10_1007_s10142_023_00996_3 crossref_primary_10_1111_cas_16193 |
| Cites_doi | 10.4049/jimmunol.1202088 10.1016/j.jcmgh.2018.09.008 10.1038/leu.2012.215 10.1016/S0140-6736(17)31827-5 10.1016/j.annonc.2019.10.018 10.1016/j.imbio.2013.07.003 10.1371/journal.ppat.1004663 10.1158/0008-5472.CAN-14-3362 10.1016/S0140-6736(17)33326-3 10.1016/j.pathophys.2017.05.004 10.1038/s41368-020-0084-8 10.1038/s41568-018-0007-6 10.4049/jimmunol.0900092 10.1016/j.lfs.2020.118513 10.3322/caac.21492 10.1186/2051-1426-1-10 10.1038/nri3901 10.1371/journal.ppat.1007468 10.1016/j.ccr.2011.12.028 10.1080/2162402X.2018.1469594 10.1186/s40425-019-0783-x 10.2174/1568009611313020002 10.1016/j.ejca.2020.02.002 10.1158/0008-5472.CAN-09-3767 10.18632/oncotarget.26473 10.4049/jimmunol.181.8.5791 10.4161/21624011.2014.954829 10.1038/nature21676 10.1002/0471142735.im0732s99 10.1016/j.jcmgh.2016.05.004 10.15252/embj.201798311 10.3389/fonc.2019.01320 10.1053/j.gastro.2015.12.042 10.1210/en.2013-1483 10.1186/bcr2903 10.1001/jamaoncol.2018.0013 10.1172/JCI82529 10.1186/s13045-019-0754-1 10.1053/j.gastro.2012.01.029 10.1111/hel.12152 10.4049/jimmunol.1000901 10.1158/1078-0432.CCR-08-1332 10.1158/1078-0432.CCR-19-0104 10.1038/s41568-018-0074-8 10.1007/978-1-4939-8600-2_16 10.1136/gutjnl-2019-318817 10.1038/labinvest.2012.148 10.1007/978-3-642-54490-3_12 10.1080/2162402X.2018.1494113 10.1016/j.brainresprot.2004.04.001 10.1136/gutjnl-2016-312078 10.1016/j.ccr.2007.05.008 10.2217/fon-2018-0581 10.1038/s41586-019-1593-5 |
| ContentType | Journal Article |
| Copyright | 2021 Copyright © 2021. Published by Elsevier B.V. Copyright Elsevier Limited Oct 10, 2021 |
| Copyright_xml | – notice: 2021 – notice: Copyright © 2021. Published by Elsevier B.V. – notice: Copyright Elsevier Limited Oct 10, 2021 |
| DBID | AAYXX CITATION CGR CUY CVF ECM EIF NPM 7TO 7U9 H94 K9. NAPCQ 7X8 5PM |
| DOI | 10.1016/j.canlet.2021.06.007 |
| DatabaseName | CrossRef Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed Oncogenes and Growth Factors Abstracts Virology and AIDS Abstracts AIDS and Cancer Research Abstracts ProQuest Health & Medical Complete (Alumni) Nursing & Allied Health Premium MEDLINE - Academic PubMed Central (Full Participant titles) |
| DatabaseTitle | CrossRef MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) AIDS and Cancer Research Abstracts ProQuest Health & Medical Complete (Alumni) Nursing & Allied Health Premium Virology and AIDS Abstracts Oncogenes and Growth Factors Abstracts MEDLINE - Academic |
| DatabaseTitleList | MEDLINE AIDS and Cancer Research Abstracts MEDLINE - Academic |
| Database_xml | – sequence: 1 dbid: NPM name: PubMed url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: EIF name: MEDLINE url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search sourceTypes: Index Database |
| DeliveryMethod | fulltext_linktorsrc |
| Discipline | Medicine |
| EISSN | 1872-7980 |
| EndPage | 71 |
| ExternalDocumentID | PMC8606306 34126195 10_1016_j_canlet_2021_06_007 S0304383521002925 |
| Genre | Research Support, Non-U.S. Gov't Journal Article Research Support, N.I.H., Extramural |
| GrantInformation_xml | – fundername: NIDDK NIH HHS grantid: R01 DK083402 – fundername: NIAID NIH HHS grantid: U19 AI116491 – fundername: NIDDK NIH HHS grantid: R01 DK118563 – fundername: NIDDK NIH HHS grantid: P30 DK078392 – fundername: NCI NIH HHS grantid: P30 CA023074 |
| GroupedDBID | --- --K --M .1- .FO .~1 0R~ 1B1 1P~ 1RT 1~. 1~5 29B 4.4 457 4CK 4G. 5GY 5RE 5VS 6J9 6PF 7-5 71M 8FE 8FH 8P~ 9JM AABNK AAEDT AAEDW AAIKJ AAKOC AALRI AAOAW AAQFI AATTM AAWTL AAXKI AAXUO AAYWO ABBQC ABFNM ABFRF ABGSF ABJNI ABMAC ABMZM ABUDA ACDAQ ACGFO ACGFS ACIEU ACIUM ACPRK ACRLP ACVFH ADBBV ADCNI ADEZE ADFRT ADUVX AEBSH AEFWE AEHWI AEIPS AEKER AENEX AEUPX AEVXI AFPUW AFRAH AFRHN AFTJW AFXIZ AGCQF AGHFR AGUBO AGYEJ AHHHB AHMBA AIEXJ AIGII AIIUN AIKHN AITUG AJRQY AJUYK AKBMS AKRWK AKYEP ALMA_UNASSIGNED_HOLDINGS AMRAJ ANKPU ANZVX APXCP AXJTR BKEYQ BKOJK BLXMC BNPGV BPHCQ BVXVI CS3 DU5 EBS EFJIC EFKBS EO8 EO9 EP2 EP3 F5P FDB FIRID FNPLU FYGXN G-Q GBLVA IH2 IHE J1W K-O KOM LK8 M29 M41 MO0 N9A O-L O9- OAUVE OC~ OO- OZT P-8 P-9 P2P PC. PQQKQ PROAC Q38 ROL RPZ SCC SDF SDG SDP SEL SES SPCBC SSH SSU SSZ T5K Z5R ~G- 7RV 7X7 8C1 AACTN AAIAV ABLVK ABYKQ AFCTW AFKRA AFKWA AJOXV AMFUW AZQEC BBNVY BENPR DOVZS EFLBG HCIFZ LCYCR M2M M2O M7P .55 .GJ 3O- 53G AAQXK AAYXX ABWVN ABXDB ACRPL ADMUD ADNMO AFFNX AFJKZ AGQPQ AGRDE AGRNS AI. ASPBG AVWKF AZFZN CITATION EJD FEDTE FGOYB G-2 HED HMK HMO HVGLF HZ~ R2- RIG SAE SEW UDS VH1 WUQ X7M ZGI CGR CUY CVF ECM EIF NPM 7TO 7U9 H94 K9. NAPCQ 7X8 5PM |
| ID | FETCH-LOGICAL-c544t-d047447aec92dbf0389683c8b94ec6eb03ff4540ccb67c436af943ecdc6d5b4f3 |
| IEDL.DBID | .~1 |
| ISSN | 0304-3835 1872-7980 |
| IngestDate | Thu Aug 21 13:57:57 EDT 2025 Fri Jul 11 07:32:00 EDT 2025 Wed Aug 13 06:37:53 EDT 2025 Thu Apr 03 07:05:57 EDT 2025 Tue Jul 01 02:29:44 EDT 2025 Thu Apr 24 22:52:22 EDT 2025 Fri Feb 23 02:43:24 EST 2024 Tue Aug 26 16:33:40 EDT 2025 |
| IsDoiOpenAccess | false |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Keywords | Sonic hedgehog Tumor microenvironment Myeloid derived suppressor cells Cytotoxic T lymphocytes |
| Language | English |
| License | Copyright © 2021. Published by Elsevier B.V. |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-c544t-d047447aec92dbf0389683c8b94ec6eb03ff4540ccb67c436af943ecdc6d5b4f3 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 These authors contributed equally |
| ORCID | 0000-0002-8997-5909 0000-0002-6559-8184 0000-0002-1266-6470 0000-0002-2490-6478 0000-0003-2265-4657 |
| OpenAccessLink | https://www.ncbi.nlm.nih.gov/pmc/articles/8606306 |
| PMID | 34126195 |
| PQID | 2558083195 |
| PQPubID | 2031080 |
| PageCount | 13 |
| ParticipantIDs | pubmedcentral_primary_oai_pubmedcentral_nih_gov_8606306 proquest_miscellaneous_2541321482 proquest_journals_2558083195 pubmed_primary_34126195 crossref_primary_10_1016_j_canlet_2021_06_007 crossref_citationtrail_10_1016_j_canlet_2021_06_007 elsevier_sciencedirect_doi_10_1016_j_canlet_2021_06_007 elsevier_clinicalkey_doi_10_1016_j_canlet_2021_06_007 |
| ProviderPackageCode | CITATION AAYXX |
| PublicationCentury | 2000 |
| PublicationDate | 2021-10-10 |
| PublicationDateYYYYMMDD | 2021-10-10 |
| PublicationDate_xml | – month: 10 year: 2021 text: 2021-10-10 day: 10 |
| PublicationDecade | 2020 |
| PublicationPlace | Ireland |
| PublicationPlace_xml | – name: Ireland – name: Clare |
| PublicationTitle | Cancer letters |
| PublicationTitleAlternate | Cancer Lett |
| PublicationYear | 2021 |
| Publisher | Elsevier B.V Elsevier Limited |
| Publisher_xml | – name: Elsevier B.V – name: Elsevier Limited |
| References | Schumacher, Feng, Aihara, Engevik, Montrose, Ottemann, Zavros (bib5) 2015; 20 Kawazoe, Yamaguchi, Yasui, Negoro, Azuma, Amagai, Hara, Baba, Tsuda, Hosaka, Kawakami, Oshima, Omuro, Machida, Esaki, Yoshida, Nishina, Komatsu, Han, Shiratori, Shitara (bib19) 2020; 129 Badary, Rahma, Ashmawy, Hafez (bib11) 2017; 24 Topalian, Taube, Pardoll (bib14) 2020 Wesolowski, Markowitz, Carson (bib26) 2013; 1 Smyth, Knodler, Giraut, Mauer, Nilsson, Van Grieken, Wagner, Moehler, Lordick (bib20) 2019; 9 Lu, Horner, Paul, Shang, Troncoso, Deng, Jiang, Chang, Spring, Sharma, Zebala, Maeda, Wang, DePinho (bib49) 2017; 543 Lechner, Liebertz, Epstein (bib34) 2010; 185 Chakrabarti, Holokai, Syu, Steele, Chang, Wang, Ahmed, Dlugosz, Zavros (bib7) 2018; 9 Chakrabarti, Holokai, Syu, Steele, Chang, Dlugosz, Zavros (bib30) 2018; 1817 Bray, Ferlay, Soerjomataram, Siegel, Torre, Jemal (bib1) 2018; 68 Wang, Song, Wang, Ji, Li, Liu, Yan (bib25) 2018; 7 Bertaux-Skeirik, Feng, Schumacher, Li, Mahe, Engevik, Javier, Peek, Ottemann, Orian-Rousseau, Boivin, Helmrath, Zavros (bib31) 2015; 11 Grullich (bib50) 2014; 201 Engevik, Feng, Yang, Zavros (bib36) 2013; 154 Ding, Li, Chakrabarti, Munoz, Faure-Kumar, Ocadiz-Ruiz, Razumilava, Zhang, Hayes, Sontz, Mendoza, Mahurkar, Greenson, Perez-Perez, Hanh, Zavros, Samuelson, Iliopoulos, Merchant (bib40) 2020 Allemani, Matsuda, Di Carlo, Harewood, Matz, Niksic, Bonaventure, Valkov, Johnson, Esteve, Ogunbiyi, Azevedo, Chen, Eser, Engholm, Stiller, Monnereau, Woods, Visser, Lim, Aitken, Weir, Coleman, Group (bib2) 2018; 391 Schouppe, Van Overmeire, Laoui, Keirsse, Van Ginderachter (bib22) 2013; 218 Ding, Hayes, Photenhauer, Eaton, Li, Ocadiz-Ruiz, Merchant (bib39) 2016; 126 Holokai, Chakrabarti, Broda, Chang, Hawkins, Sundaram, Wroblewski, Peek, Wang, Helmrath, Wells, Zavros (bib6) 2019; 15 Toki, Merritt, Wong, Smithy, Kluger, Syrigos, Ong, Warren, Beechem, Rimm (bib35) 2019; 25 Guertin, Sabatini (bib54) 2007; 12 Moehler, Shitara, Garrido, Salman, Shen, Wyrwicz, Yamaguchi, Skoczylas, Campos Bragagnoli, Liu, Schenker, Yanez, Tehfe, Poulart, Cullen, Lei, Kondo, Li, Ajani, Janjigian (bib58) 2020; 31 Corzo, Cotter, Cheng, Cheng, Kusmartsev, Sotomayor, Padhya, McCaffrey, McCaffrey, Gabrilovich (bib42) 2009; 182 Fuchs, Doi, Jang, Muro, Satoh, Machado, Sun, Jalal, Shah, Metges, Garrido, Golan, Mandala, Wainberg, Catenacci, Ohtsu, Shitara, Geva, Bleeker, Ko, Ku, Philip, Enzinger, Bang, Levitan, Wang, Rosales, Dalal, Yoon (bib17) 2018; 4 Moehler, Maderer, Thuss-Patience, Brenner, Meiler, Ettrich, Hofheinz, Al-Batran, Vogel, Mueller, Lutz, Lordick, Alsina, Borchert, Greil, Eisterer, Schad, Slotta-Huspenina, Van Cutsem, Lorenzen (bib57) 2020; 31 Wang, Ding, Yen, Xia, Izzo, Lang, Li, Hsu, Miller, Wang, Lee, Hsu, Huo, Labaff, Liu, Huang, Lai, Tsai, Chang, Chen, Wu, Buttar, Wang, Wu, Wang, Ajani, Hung (bib13) 2012; 21 Willet, Lewis, Miao, Liu, Radyk, Cunningham, Burclaff, Sibbel, Lo, Blanc, Davidson, Wang, Mills (bib12) 2018; 37 Draghiciu, Lubbers, Nijman, Daemen (bib45) 2015; 4 Xiao, Feng, Engevik, Martin, Tritschler, Schumacher, Koncar, Roland, Nam, Goldenring, Zavros (bib37) 2013; 93 Demaria, Cornen, Daeron, Morel, Medzhitov, Vivier (bib15) 2019; 574 Wagner, Syn, Moehler, Grothe, Yong, Tai, Ho, Unverzagt (bib3) 2017; 8 Mei, Huang, Qiao, Lam (bib46) 2020; 12 Schumacher, Donnelly, Engevik, Xiao, Yang, Kenny, Varro, Hollande, Samuelson, Zavros (bib4) 2012; 142 Ko, Zea, Rini, Ireland, Elson, Cohen, Golshayan, Rayman, Wood, Garcia, Dreicer, Bukowski, Finke (bib47) 2009; 15 Kodera, Katanasaka, Kitamura, Tsuda, Nishio, Tamura, Koizumi (bib48) 2011; 13 Kang, Boku, Satoh, Ryu, Chao, Kato, Chung, Chen, Muro, Kang, Yeh, Yoshikawa, Oh, Bai, Tamura, Lee, Hamamoto, Kim, Chin, Oh, Minashi, Cho, Tsuda, Chen (bib56) 2017; 390 Weichhart, Hengstschlager, Linke (bib55) 2015; 15 Mossmann, Park, Hall (bib53) 2018; 18 Dedhia, Bertaux-Skeirik, Zavros, Spence (bib28) 2016; 150 Youn, Nagaraj, Collazo, Gabrilovich (bib23) 2008; 181 Engevik, Feng, Choi, White, Bertaux-Skeirik, Li, Mahe, Aihara, Yang, DiPasquale, Oh, Engevik, Giraud, Montrose, Medvedovic, Helmrath, Goldenring, Zavros (bib32) 2016; 2 Poschke, Mougiakakos, Hansson, Masucci, Kiessling (bib41) 2010; 70 Nair, Archer, Tedder (bib33) 2012 Steele, Chakrabarti, Wang, Biesiada, Holokai, Chang, Nowacki, Hawkins, Mahe, Sundaram, Shroyer, Medvedovic, Helmrath, Ahmad, Zavros (bib29) 2019; 7 Bu, Ji (bib9) 2013; 13 Zhang, Velez-Delgado, Mathew, Li, Mendez, Flannagan, Rhim, Simeone, Beatty, Pasca di Magliano (bib21) 2017; 66 Mougiakakos, Jitschin, von Bahr, Poschke, Gary, Sundberg, Gerbitz, Ljungman, Le Blanc (bib43) 2013; 27 Hua, Kong, Zhang, Wang, Luo, Jiang (bib52) 2019; 12 Wang, Jia, Claxton, Ehmann, Rybka, Mineishi, Naik, Khawaja, Sivik, Han, Hohl, Zheng (bib44) 2018; 7 Daniel, DeCoster (bib38) 2004; 13 Trikha, Carson (bib51) 2014; 1846 Wang, Chang, Wong, Ong, Chong, Ling (bib24) 2013; 190 Demaria, Romano, Brackstone, Formenti (bib16) 2019; 7 Drost, Clevers (bib27) 2018; 18 Bang, Van Cutsem, Fuchs, Ohtsu, Tabernero, Ilson, Hyung, Strong, Goetze, Yoshikawa, Tang, Hwang, Webb, Adelberg, Shitara (bib18) 2019; 15 Fattahi, Amjadi-Moheb, Tabaripour, Ashrafi, Akhavan-Niaki (bib8) 2020; 262 Lastwika, Wilson, Li, Norris, Xu, Ghazarian, Kitagawa, Kawabata, Taube, Yao, Liu, Gills, Dennis (bib10) 2016; 76 Fattahi (10.1016/j.canlet.2021.06.007_bib8) 2020; 262 Topalian (10.1016/j.canlet.2021.06.007_bib14) 2020 Guertin (10.1016/j.canlet.2021.06.007_bib54) 2007; 12 Bray (10.1016/j.canlet.2021.06.007_bib1) 2018; 68 Youn (10.1016/j.canlet.2021.06.007_bib23) 2008; 181 Trikha (10.1016/j.canlet.2021.06.007_bib51) 2014; 1846 Hua (10.1016/j.canlet.2021.06.007_bib52) 2019; 12 Steele (10.1016/j.canlet.2021.06.007_bib29) 2019; 7 Bu (10.1016/j.canlet.2021.06.007_bib9) 2013; 13 Toki (10.1016/j.canlet.2021.06.007_bib35) 2019; 25 Wang (10.1016/j.canlet.2021.06.007_bib24) 2013; 190 Lastwika (10.1016/j.canlet.2021.06.007_bib10) 2016; 76 Bang (10.1016/j.canlet.2021.06.007_bib18) 2019; 15 Wang (10.1016/j.canlet.2021.06.007_bib44) 2018; 7 Engevik (10.1016/j.canlet.2021.06.007_bib36) 2013; 154 Moehler (10.1016/j.canlet.2021.06.007_bib57) 2020; 31 Wagner (10.1016/j.canlet.2021.06.007_bib3) 2017; 8 Draghiciu (10.1016/j.canlet.2021.06.007_bib45) 2015; 4 Lechner (10.1016/j.canlet.2021.06.007_bib34) 2010; 185 Lu (10.1016/j.canlet.2021.06.007_bib49) 2017; 543 Demaria (10.1016/j.canlet.2021.06.007_bib15) 2019; 574 Kawazoe (10.1016/j.canlet.2021.06.007_bib19) 2020; 129 Wang (10.1016/j.canlet.2021.06.007_bib25) 2018; 7 Ko (10.1016/j.canlet.2021.06.007_bib47) 2009; 15 Weichhart (10.1016/j.canlet.2021.06.007_bib55) 2015; 15 Mei (10.1016/j.canlet.2021.06.007_bib46) 2020; 12 Badary (10.1016/j.canlet.2021.06.007_bib11) 2017; 24 Mougiakakos (10.1016/j.canlet.2021.06.007_bib43) 2013; 27 Schumacher (10.1016/j.canlet.2021.06.007_bib5) 2015; 20 Grullich (10.1016/j.canlet.2021.06.007_bib50) 2014; 201 Chakrabarti (10.1016/j.canlet.2021.06.007_bib7) 2018; 9 Drost (10.1016/j.canlet.2021.06.007_bib27) 2018; 18 Daniel (10.1016/j.canlet.2021.06.007_bib38) 2004; 13 Moehler (10.1016/j.canlet.2021.06.007_bib58) 2020; 31 Ding (10.1016/j.canlet.2021.06.007_bib39) 2016; 126 Holokai (10.1016/j.canlet.2021.06.007_bib6) 2019; 15 Wang (10.1016/j.canlet.2021.06.007_bib13) 2012; 21 Dedhia (10.1016/j.canlet.2021.06.007_bib28) 2016; 150 Chakrabarti (10.1016/j.canlet.2021.06.007_bib30) 2018; 1817 Kodera (10.1016/j.canlet.2021.06.007_bib48) 2011; 13 Zhang (10.1016/j.canlet.2021.06.007_bib21) 2017; 66 Poschke (10.1016/j.canlet.2021.06.007_bib41) 2010; 70 Ding (10.1016/j.canlet.2021.06.007_bib40) 2020 Schouppe (10.1016/j.canlet.2021.06.007_bib22) 2013; 218 Wesolowski (10.1016/j.canlet.2021.06.007_bib26) 2013; 1 Bertaux-Skeirik (10.1016/j.canlet.2021.06.007_bib31) 2015; 11 Allemani (10.1016/j.canlet.2021.06.007_bib2) 2018; 391 Smyth (10.1016/j.canlet.2021.06.007_bib20) 2019; 9 Demaria (10.1016/j.canlet.2021.06.007_bib16) 2019; 7 Kang (10.1016/j.canlet.2021.06.007_bib56) 2017; 390 Schumacher (10.1016/j.canlet.2021.06.007_bib4) 2012; 142 Willet (10.1016/j.canlet.2021.06.007_bib12) 2018; 37 Nair (10.1016/j.canlet.2021.06.007_bib33) 2012 Mossmann (10.1016/j.canlet.2021.06.007_bib53) 2018; 18 Corzo (10.1016/j.canlet.2021.06.007_bib42) 2009; 182 Engevik (10.1016/j.canlet.2021.06.007_bib32) 2016; 2 Fuchs (10.1016/j.canlet.2021.06.007_bib17) 2018; 4 Xiao (10.1016/j.canlet.2021.06.007_bib37) 2013; 93 |
| References_xml | – volume: 13 year: 2011 ident: bib48 article-title: Sunitinib inhibits lymphatic endothelial cell functions and lymph node metastasis in a breast cancer model through inhibition of vascular endothelial growth factor receptor 3 publication-title: Breast Cancer Res. – volume: 4 year: 2018 ident: bib17 article-title: Safety and efficacy of pembrolizumab monotherapy in patients with previously treated advanced gastric and gastroesophageal junction cancer: phase 2 clinical KEYNOTE-059 trial publication-title: JAMA Oncol – volume: 66 start-page: 124 year: 2017 end-page: 136 ident: bib21 article-title: Myeloid cells are required for PD-1/PD-L1 checkpoint activation and the establishment of an immunosuppressive environment in pancreatic cancer publication-title: Gut – volume: 12 start-page: 16 year: 2020 ident: bib46 article-title: Immune checkpoint pathways in immunotherapy for head and neck squamous cell carcinoma publication-title: Int. J. Oral Sci. – volume: 4 year: 2015 ident: bib45 article-title: Myeloid derived suppressor cells-An overview of combat strategies to increase immunotherapy efficacy publication-title: OncoImmunology – volume: 15 start-page: 599 year: 2015 end-page: 614 ident: bib55 article-title: Regulation of innate immune cell function by mTOR publication-title: Nat. Rev. Immunol. – volume: 7 start-page: 161 year: 2019 end-page: 184 ident: bib29 article-title: An organoid-based preclinical model of human gastric cancer publication-title: Cell Mol Gastroenterol Hepatol – volume: 154 start-page: 4627 year: 2013 end-page: 4639 ident: bib36 article-title: The Acid-secreting parietal cell as an endocrine source of sonic hedgehog during gastric repair publication-title: Endocrinology – volume: 21 start-page: 374 year: 2012 end-page: 387 ident: bib13 article-title: The crosstalk of mTOR/S6K1 and Hedgehog pathways publication-title: Canc. Cell – volume: 31 start-page: 228 year: 2020 end-page: 235 ident: bib57 article-title: Cisplatin and 5-fluorouracil with or without epidermal growth factor receptor inhibition panitumumab for patients with non-resectable, advanced or metastatic oesophageal squamous cell cancer: a prospective, open-label, randomised phase III AIO/EORTC trial (POWER) publication-title: Ann. Oncol. – volume: 1 start-page: 10 year: 2013 ident: bib26 article-title: Myeloid derived suppressor cells - a new therapeutic target in the treatment of cancer publication-title: J Immunother Cancer – volume: 37 year: 2018 ident: bib12 article-title: Regenerative proliferation of differentiated cells by mTORC1-dependent paligenosis publication-title: EMBO J. – volume: 182 start-page: 5693 year: 2009 end-page: 5701 ident: bib42 article-title: Mechanism regulating reactive oxygen species in tumor-induced myeloid-derived suppressor cells publication-title: J. Immunol. – volume: 7 year: 2018 ident: bib44 article-title: VISTA is highly expressed on MDSCs and mediates an inhibition of T cell response in patients with AML publication-title: OncoImmunology – volume: 150 start-page: 1098 year: 2016 end-page: 1112 ident: bib28 article-title: Organoid models of human gastrointestinal development and disease publication-title: Gastroenterology – volume: 15 year: 2019 ident: bib6 article-title: Increased programmed death-ligand 1 is an early epithelial cell response to Helicobacter pylori infection publication-title: PLoS Pathog. – volume: 574 start-page: 45 year: 2019 end-page: 56 ident: bib15 article-title: Harnessing innate immunity in cancer therapy publication-title: Nature – volume: 12 start-page: 9 year: 2007 end-page: 22 ident: bib54 article-title: Defining the role of mTOR in cancer publication-title: Canc. Cell – volume: 390 start-page: 2461 year: 2017 end-page: 2471 ident: bib56 article-title: Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2): a randomised, double-blind, placebo-controlled, phase 3 trial publication-title: Lancet – volume: 70 start-page: 4335 year: 2010 end-page: 4345 ident: bib41 article-title: Immature immunosuppressive CD14+HLA-DR-/low cells in melanoma patients are Stat3hi and overexpress CD80, CD83, and DC-sign publication-title: Canc. Res. – volume: 13 start-page: 144 year: 2004 end-page: 150 ident: bib38 article-title: Quantification of sPLA2-induced early and late apoptosis changes in neuronal cell cultures using combined TUNEL and DAPI staining publication-title: Brain Res Brain Res Protoc – volume: 543 start-page: 728 year: 2017 end-page: 732 ident: bib49 article-title: Effective combinatorial immunotherapy for castration-resistant prostate cancer publication-title: Nature – start-page: 367 year: 2020 ident: bib14 article-title: Neoadjuvant checkpoint blockade for cancer immunotherapy publication-title: Science – volume: 9 start-page: 37439 year: 2018 end-page: 37457 ident: bib7 article-title: Hedgehog signaling induces PD-L1 expression and tumor cell proliferation in gastric cancer publication-title: Oncotarget – volume: 12 start-page: 71 year: 2019 ident: bib52 article-title: Targeting mTOR for cancer therapy publication-title: J. Hematol. Oncol. – volume: 20 start-page: 19 year: 2015 end-page: 28 ident: bib5 article-title: Helicobacter pylori-induced Sonic Hedgehog expression is regulated by NFkappaB pathway activation: the use of a novel in vitro model to study epithelial response to infection publication-title: Helicobacter – volume: 18 start-page: 744 year: 2018 end-page: 757 ident: bib53 article-title: mTOR signalling and cellular metabolism are mutual determinants in cancer publication-title: Nat. Rev. Canc. – volume: 201 start-page: 207 year: 2014 end-page: 214 ident: bib50 article-title: Cabozantinib: a MET, RET, and VEGFR2 tyrosine kinase inhibitor publication-title: Recent Results Canc. Res. – volume: 25 start-page: 5503 year: 2019 end-page: 5512 ident: bib35 article-title: High-plex predictive marker discovery for melanoma immunotherapy-treated patients using digital spatial profiling publication-title: Clin. Canc. Res. – volume: 1846 start-page: 55 year: 2014 end-page: 65 ident: bib51 article-title: Signaling pathways involved in MDSC regulation publication-title: Biochim. Biophys. Acta – volume: 2 start-page: 605 year: 2016 end-page: 624 ident: bib32 article-title: The development of spasmolytic polypeptide/TFF2-expressing metaplasia (SPEM) during gastric repair is absent in the aged stomach publication-title: Cell Mol Gastroenterol Hepatol – volume: 24 start-page: 205 year: 2017 end-page: 211 ident: bib11 article-title: H. Pylori infection increases gastric mucosal COX2 and mTOR expression in chronic gastritis: implications for cancer progression? publication-title: Pathophysiology – volume: 76 start-page: 227 year: 2016 end-page: 238 ident: bib10 article-title: Control of PD-L1 expression by oncogenic activation of the AKT-mTOR pathway in non-small cell lung cancer publication-title: Canc. Res. – volume: 18 start-page: 407 year: 2018 end-page: 418 ident: bib27 article-title: Organoids in cancer research publication-title: Nat. Rev. Canc. – volume: 190 start-page: 794 year: 2013 end-page: 804 ident: bib24 article-title: Increased myeloid-derived suppressor cells in gastric cancer correlate with cancer stage and plasma S100A8/A9 proinflammatory proteins publication-title: J. Immunol. – volume: 129 start-page: 97 year: 2020 end-page: 106 ident: bib19 article-title: Safety and efficacy of pembrolizumab in combination with S-1 plus oxaliplatin as a first-line treatment in patients with advanced gastric/gastroesophageal junction cancer: cohort 1 data from the KEYNOTE-659 phase IIb study publication-title: Eur. J. Canc. – volume: 27 start-page: 377 year: 2013 end-page: 388 ident: bib43 article-title: Immunosuppressive CD14+HLA-DRlow/neg Ido+ myeloid cells in patients following allogeneic hematopoietic stem cell transplantation publication-title: Leukemia – volume: 9 start-page: 1320 year: 2019 ident: bib20 article-title: VESTIGE: adjuvant immunotherapy in patients with resected esophageal, gastroesophageal junction and gastric cancer following preoperative chemotherapy with high risk for recurrence (N+ and/or R1): an open label randomized controlled phase-2-study publication-title: Front Oncol – volume: 391 start-page: 1023 year: 2018 end-page: 1075 ident: bib2 article-title: Global surveillance of trends in cancer survival 2000-14 (CONCORD-3): analysis of individual records for 37 513 025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries publication-title: Lancet – volume: 13 start-page: 121 year: 2013 end-page: 125 ident: bib9 article-title: Therapeutic implications of mTOR inhibitors in the treatment of gastric cancer publication-title: Curr. Cancer Drug Targets – year: 2020 ident: bib40 article-title: MiR130b from Schlafen4(+) MDSCs stimulates epithelial proliferation and correlates with preneoplastic changes prior to gastric cancer publication-title: Gut – volume: 15 start-page: 943 year: 2019 end-page: 952 ident: bib18 article-title: KEYNOTE-585: phase III study of perioperative chemotherapy with or without pembrolizumab for gastric cancer publication-title: Future Oncol. – volume: 15 start-page: 2148 year: 2009 end-page: 2157 ident: bib47 article-title: Sunitinib mediates reversal of myeloid-derived suppressor cell accumulation in renal cell carcinoma patients publication-title: Clin. Canc. Res. – volume: 185 start-page: 2273 year: 2010 end-page: 2284 ident: bib34 article-title: Characterization of cytokine-induced myeloid-derived suppressor cells from normal human peripheral blood mononuclear cells publication-title: J. Immunol. – volume: 1817 start-page: 157 year: 2018 end-page: 168 ident: bib30 article-title: Mouse-derived gastric organoid and immune cell Co-culture for the study of the tumor microenvironment publication-title: Methods Mol. Biol. – volume: 31 start-page: S1142 year: 2020 end-page: S1215 ident: bib58 article-title: ESMO virtual congress publication-title: Ann. Oncol. – volume: 142 start-page: 1150 year: 2012 end-page: 1159 ident: bib4 article-title: Gastric sonic hedgehog acts as a macrophage chemoattractant during the immune response to Helicobacter pylori publication-title: Gastroenterology – volume: 181 start-page: 5791 year: 2008 end-page: 5802 ident: bib23 article-title: Subsets of myeloid-derived suppressor cells in tumor-bearing mice publication-title: J. Immunol. – volume: 93 start-page: 96 year: 2013 end-page: 111 ident: bib37 article-title: Sonic Hedgehog contributes to gastric mucosal restitution after injury publication-title: Lab. Invest. – volume: 7 year: 2018 ident: bib25 article-title: Prognostic role of pretreatment circulating MDSCs in patients with solid malignancies: a meta-analysis of 40 studies publication-title: OncoImmunology – year: 2012 ident: bib33 article-title: Isolation and generation of human dendritic cells publication-title: Curr. Protoc. Im. – volume: 68 start-page: 394 year: 2018 end-page: 424 ident: bib1 article-title: Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries publication-title: CA Cancer J Clin – volume: 11 year: 2015 ident: bib31 article-title: CD44 plays a functional role in Helicobacter pylori-induced epithelial cell proliferation publication-title: PLoS Pathog. – volume: 126 start-page: 2867 year: 2016 end-page: 2880 ident: bib39 article-title: Schlafen 4-expressing myeloid-derived suppressor cells are induced during murine gastric metaplasia publication-title: J. Clin. Invest. – volume: 218 start-page: 1385 year: 2013 end-page: 1391 ident: bib22 article-title: Modulation of CD8(+) T-cell activation events by monocytic and granulocytic myeloid-derived suppressor cells publication-title: Immunobiology – volume: 262 year: 2020 ident: bib8 article-title: PI3K/AKT/mTOR signaling in gastric cancer: epigenetics and beyond publication-title: Life Sci. – volume: 7 start-page: 318 year: 2019 ident: bib16 article-title: Immune induction strategies to enhance responses to PD-1 blockade: lessons from the TONIC trial publication-title: J Immunother Cancer – volume: 8 year: 2017 ident: bib3 article-title: Chemotherapy for advanced gastric cancer publication-title: Cochrane Database Syst. Rev. – volume: 190 start-page: 794 year: 2013 ident: 10.1016/j.canlet.2021.06.007_bib24 article-title: Increased myeloid-derived suppressor cells in gastric cancer correlate with cancer stage and plasma S100A8/A9 proinflammatory proteins publication-title: J. Immunol. doi: 10.4049/jimmunol.1202088 – volume: 7 start-page: 161 year: 2019 ident: 10.1016/j.canlet.2021.06.007_bib29 article-title: An organoid-based preclinical model of human gastric cancer publication-title: Cell Mol Gastroenterol Hepatol doi: 10.1016/j.jcmgh.2018.09.008 – volume: 27 start-page: 377 year: 2013 ident: 10.1016/j.canlet.2021.06.007_bib43 article-title: Immunosuppressive CD14+HLA-DRlow/neg Ido+ myeloid cells in patients following allogeneic hematopoietic stem cell transplantation publication-title: Leukemia doi: 10.1038/leu.2012.215 – volume: 390 start-page: 2461 year: 2017 ident: 10.1016/j.canlet.2021.06.007_bib56 article-title: Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2): a randomised, double-blind, placebo-controlled, phase 3 trial publication-title: Lancet doi: 10.1016/S0140-6736(17)31827-5 – volume: 31 start-page: 228 year: 2020 ident: 10.1016/j.canlet.2021.06.007_bib57 publication-title: Ann. Oncol. doi: 10.1016/j.annonc.2019.10.018 – volume: 218 start-page: 1385 year: 2013 ident: 10.1016/j.canlet.2021.06.007_bib22 article-title: Modulation of CD8(+) T-cell activation events by monocytic and granulocytic myeloid-derived suppressor cells publication-title: Immunobiology doi: 10.1016/j.imbio.2013.07.003 – volume: 11 year: 2015 ident: 10.1016/j.canlet.2021.06.007_bib31 article-title: CD44 plays a functional role in Helicobacter pylori-induced epithelial cell proliferation publication-title: PLoS Pathog. doi: 10.1371/journal.ppat.1004663 – volume: 76 start-page: 227 year: 2016 ident: 10.1016/j.canlet.2021.06.007_bib10 article-title: Control of PD-L1 expression by oncogenic activation of the AKT-mTOR pathway in non-small cell lung cancer publication-title: Canc. Res. doi: 10.1158/0008-5472.CAN-14-3362 – volume: 391 start-page: 1023 year: 2018 ident: 10.1016/j.canlet.2021.06.007_bib2 article-title: Global surveillance of trends in cancer survival 2000-14 (CONCORD-3): analysis of individual records for 37 513 025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries publication-title: Lancet doi: 10.1016/S0140-6736(17)33326-3 – volume: 24 start-page: 205 year: 2017 ident: 10.1016/j.canlet.2021.06.007_bib11 article-title: H. Pylori infection increases gastric mucosal COX2 and mTOR expression in chronic gastritis: implications for cancer progression? publication-title: Pathophysiology doi: 10.1016/j.pathophys.2017.05.004 – volume: 12 start-page: 16 year: 2020 ident: 10.1016/j.canlet.2021.06.007_bib46 article-title: Immune checkpoint pathways in immunotherapy for head and neck squamous cell carcinoma publication-title: Int. J. Oral Sci. doi: 10.1038/s41368-020-0084-8 – volume: 18 start-page: 407 year: 2018 ident: 10.1016/j.canlet.2021.06.007_bib27 article-title: Organoids in cancer research publication-title: Nat. Rev. Canc. doi: 10.1038/s41568-018-0007-6 – volume: 182 start-page: 5693 year: 2009 ident: 10.1016/j.canlet.2021.06.007_bib42 article-title: Mechanism regulating reactive oxygen species in tumor-induced myeloid-derived suppressor cells publication-title: J. Immunol. doi: 10.4049/jimmunol.0900092 – volume: 262 year: 2020 ident: 10.1016/j.canlet.2021.06.007_bib8 article-title: PI3K/AKT/mTOR signaling in gastric cancer: epigenetics and beyond publication-title: Life Sci. doi: 10.1016/j.lfs.2020.118513 – volume: 68 start-page: 394 year: 2018 ident: 10.1016/j.canlet.2021.06.007_bib1 article-title: Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries publication-title: CA Cancer J Clin doi: 10.3322/caac.21492 – start-page: 367 year: 2020 ident: 10.1016/j.canlet.2021.06.007_bib14 article-title: Neoadjuvant checkpoint blockade for cancer immunotherapy publication-title: Science – volume: 1 start-page: 10 year: 2013 ident: 10.1016/j.canlet.2021.06.007_bib26 article-title: Myeloid derived suppressor cells - a new therapeutic target in the treatment of cancer publication-title: J Immunother Cancer doi: 10.1186/2051-1426-1-10 – volume: 15 start-page: 599 year: 2015 ident: 10.1016/j.canlet.2021.06.007_bib55 article-title: Regulation of innate immune cell function by mTOR publication-title: Nat. Rev. Immunol. doi: 10.1038/nri3901 – volume: 15 year: 2019 ident: 10.1016/j.canlet.2021.06.007_bib6 article-title: Increased programmed death-ligand 1 is an early epithelial cell response to Helicobacter pylori infection publication-title: PLoS Pathog. doi: 10.1371/journal.ppat.1007468 – volume: 21 start-page: 374 year: 2012 ident: 10.1016/j.canlet.2021.06.007_bib13 article-title: The crosstalk of mTOR/S6K1 and Hedgehog pathways publication-title: Canc. Cell doi: 10.1016/j.ccr.2011.12.028 – volume: 7 year: 2018 ident: 10.1016/j.canlet.2021.06.007_bib44 article-title: VISTA is highly expressed on MDSCs and mediates an inhibition of T cell response in patients with AML publication-title: OncoImmunology doi: 10.1080/2162402X.2018.1469594 – volume: 7 start-page: 318 year: 2019 ident: 10.1016/j.canlet.2021.06.007_bib16 article-title: Immune induction strategies to enhance responses to PD-1 blockade: lessons from the TONIC trial publication-title: J Immunother Cancer doi: 10.1186/s40425-019-0783-x – volume: 13 start-page: 121 year: 2013 ident: 10.1016/j.canlet.2021.06.007_bib9 article-title: Therapeutic implications of mTOR inhibitors in the treatment of gastric cancer publication-title: Curr. Cancer Drug Targets doi: 10.2174/1568009611313020002 – volume: 129 start-page: 97 year: 2020 ident: 10.1016/j.canlet.2021.06.007_bib19 article-title: Safety and efficacy of pembrolizumab in combination with S-1 plus oxaliplatin as a first-line treatment in patients with advanced gastric/gastroesophageal junction cancer: cohort 1 data from the KEYNOTE-659 phase IIb study publication-title: Eur. J. Canc. doi: 10.1016/j.ejca.2020.02.002 – volume: 70 start-page: 4335 year: 2010 ident: 10.1016/j.canlet.2021.06.007_bib41 article-title: Immature immunosuppressive CD14+HLA-DR-/low cells in melanoma patients are Stat3hi and overexpress CD80, CD83, and DC-sign publication-title: Canc. Res. doi: 10.1158/0008-5472.CAN-09-3767 – volume: 9 start-page: 37439 year: 2018 ident: 10.1016/j.canlet.2021.06.007_bib7 article-title: Hedgehog signaling induces PD-L1 expression and tumor cell proliferation in gastric cancer publication-title: Oncotarget doi: 10.18632/oncotarget.26473 – volume: 181 start-page: 5791 year: 2008 ident: 10.1016/j.canlet.2021.06.007_bib23 article-title: Subsets of myeloid-derived suppressor cells in tumor-bearing mice publication-title: J. Immunol. doi: 10.4049/jimmunol.181.8.5791 – volume: 4 year: 2015 ident: 10.1016/j.canlet.2021.06.007_bib45 article-title: Myeloid derived suppressor cells-An overview of combat strategies to increase immunotherapy efficacy publication-title: OncoImmunology doi: 10.4161/21624011.2014.954829 – volume: 543 start-page: 728 year: 2017 ident: 10.1016/j.canlet.2021.06.007_bib49 article-title: Effective combinatorial immunotherapy for castration-resistant prostate cancer publication-title: Nature doi: 10.1038/nature21676 – year: 2012 ident: 10.1016/j.canlet.2021.06.007_bib33 article-title: Isolation and generation of human dendritic cells publication-title: Curr. Protoc. Im. doi: 10.1002/0471142735.im0732s99 – volume: 2 start-page: 605 year: 2016 ident: 10.1016/j.canlet.2021.06.007_bib32 article-title: The development of spasmolytic polypeptide/TFF2-expressing metaplasia (SPEM) during gastric repair is absent in the aged stomach publication-title: Cell Mol Gastroenterol Hepatol doi: 10.1016/j.jcmgh.2016.05.004 – volume: 37 year: 2018 ident: 10.1016/j.canlet.2021.06.007_bib12 article-title: Regenerative proliferation of differentiated cells by mTORC1-dependent paligenosis publication-title: EMBO J. doi: 10.15252/embj.201798311 – volume: 9 start-page: 1320 year: 2019 ident: 10.1016/j.canlet.2021.06.007_bib20 article-title: VESTIGE: adjuvant immunotherapy in patients with resected esophageal, gastroesophageal junction and gastric cancer following preoperative chemotherapy with high risk for recurrence (N+ and/or R1): an open label randomized controlled phase-2-study publication-title: Front Oncol doi: 10.3389/fonc.2019.01320 – volume: 150 start-page: 1098 year: 2016 ident: 10.1016/j.canlet.2021.06.007_bib28 article-title: Organoid models of human gastrointestinal development and disease publication-title: Gastroenterology doi: 10.1053/j.gastro.2015.12.042 – volume: 154 start-page: 4627 year: 2013 ident: 10.1016/j.canlet.2021.06.007_bib36 article-title: The Acid-secreting parietal cell as an endocrine source of sonic hedgehog during gastric repair publication-title: Endocrinology doi: 10.1210/en.2013-1483 – volume: 13 year: 2011 ident: 10.1016/j.canlet.2021.06.007_bib48 article-title: Sunitinib inhibits lymphatic endothelial cell functions and lymph node metastasis in a breast cancer model through inhibition of vascular endothelial growth factor receptor 3 publication-title: Breast Cancer Res. doi: 10.1186/bcr2903 – volume: 4 year: 2018 ident: 10.1016/j.canlet.2021.06.007_bib17 article-title: Safety and efficacy of pembrolizumab monotherapy in patients with previously treated advanced gastric and gastroesophageal junction cancer: phase 2 clinical KEYNOTE-059 trial publication-title: JAMA Oncol doi: 10.1001/jamaoncol.2018.0013 – volume: 126 start-page: 2867 year: 2016 ident: 10.1016/j.canlet.2021.06.007_bib39 article-title: Schlafen 4-expressing myeloid-derived suppressor cells are induced during murine gastric metaplasia publication-title: J. Clin. Invest. doi: 10.1172/JCI82529 – volume: 12 start-page: 71 year: 2019 ident: 10.1016/j.canlet.2021.06.007_bib52 article-title: Targeting mTOR for cancer therapy publication-title: J. Hematol. Oncol. doi: 10.1186/s13045-019-0754-1 – volume: 142 start-page: 1150 year: 2012 ident: 10.1016/j.canlet.2021.06.007_bib4 article-title: Gastric sonic hedgehog acts as a macrophage chemoattractant during the immune response to Helicobacter pylori publication-title: Gastroenterology doi: 10.1053/j.gastro.2012.01.029 – volume: 20 start-page: 19 year: 2015 ident: 10.1016/j.canlet.2021.06.007_bib5 article-title: Helicobacter pylori-induced Sonic Hedgehog expression is regulated by NFkappaB pathway activation: the use of a novel in vitro model to study epithelial response to infection publication-title: Helicobacter doi: 10.1111/hel.12152 – volume: 1846 start-page: 55 year: 2014 ident: 10.1016/j.canlet.2021.06.007_bib51 article-title: Signaling pathways involved in MDSC regulation publication-title: Biochim. Biophys. Acta – volume: 185 start-page: 2273 year: 2010 ident: 10.1016/j.canlet.2021.06.007_bib34 article-title: Characterization of cytokine-induced myeloid-derived suppressor cells from normal human peripheral blood mononuclear cells publication-title: J. Immunol. doi: 10.4049/jimmunol.1000901 – volume: 15 start-page: 2148 year: 2009 ident: 10.1016/j.canlet.2021.06.007_bib47 article-title: Sunitinib mediates reversal of myeloid-derived suppressor cell accumulation in renal cell carcinoma patients publication-title: Clin. Canc. Res. doi: 10.1158/1078-0432.CCR-08-1332 – volume: 25 start-page: 5503 year: 2019 ident: 10.1016/j.canlet.2021.06.007_bib35 article-title: High-plex predictive marker discovery for melanoma immunotherapy-treated patients using digital spatial profiling publication-title: Clin. Canc. Res. doi: 10.1158/1078-0432.CCR-19-0104 – volume: 18 start-page: 744 year: 2018 ident: 10.1016/j.canlet.2021.06.007_bib53 article-title: mTOR signalling and cellular metabolism are mutual determinants in cancer publication-title: Nat. Rev. Canc. doi: 10.1038/s41568-018-0074-8 – volume: 1817 start-page: 157 year: 2018 ident: 10.1016/j.canlet.2021.06.007_bib30 article-title: Mouse-derived gastric organoid and immune cell Co-culture for the study of the tumor microenvironment publication-title: Methods Mol. Biol. doi: 10.1007/978-1-4939-8600-2_16 – year: 2020 ident: 10.1016/j.canlet.2021.06.007_bib40 article-title: MiR130b from Schlafen4(+) MDSCs stimulates epithelial proliferation and correlates with preneoplastic changes prior to gastric cancer publication-title: Gut doi: 10.1136/gutjnl-2019-318817 – volume: 93 start-page: 96 year: 2013 ident: 10.1016/j.canlet.2021.06.007_bib37 article-title: Sonic Hedgehog contributes to gastric mucosal restitution after injury publication-title: Lab. Invest. doi: 10.1038/labinvest.2012.148 – volume: 201 start-page: 207 year: 2014 ident: 10.1016/j.canlet.2021.06.007_bib50 article-title: Cabozantinib: a MET, RET, and VEGFR2 tyrosine kinase inhibitor publication-title: Recent Results Canc. Res. doi: 10.1007/978-3-642-54490-3_12 – volume: 7 year: 2018 ident: 10.1016/j.canlet.2021.06.007_bib25 article-title: Prognostic role of pretreatment circulating MDSCs in patients with solid malignancies: a meta-analysis of 40 studies publication-title: OncoImmunology doi: 10.1080/2162402X.2018.1494113 – volume: 31 start-page: S1142 year: 2020 ident: 10.1016/j.canlet.2021.06.007_bib58 article-title: ESMO virtual congress publication-title: Ann. Oncol. – volume: 8 year: 2017 ident: 10.1016/j.canlet.2021.06.007_bib3 article-title: Chemotherapy for advanced gastric cancer publication-title: Cochrane Database Syst. Rev. – volume: 13 start-page: 144 year: 2004 ident: 10.1016/j.canlet.2021.06.007_bib38 article-title: Quantification of sPLA2-induced early and late apoptosis changes in neuronal cell cultures using combined TUNEL and DAPI staining publication-title: Brain Res Brain Res Protoc doi: 10.1016/j.brainresprot.2004.04.001 – volume: 66 start-page: 124 year: 2017 ident: 10.1016/j.canlet.2021.06.007_bib21 article-title: Myeloid cells are required for PD-1/PD-L1 checkpoint activation and the establishment of an immunosuppressive environment in pancreatic cancer publication-title: Gut doi: 10.1136/gutjnl-2016-312078 – volume: 12 start-page: 9 year: 2007 ident: 10.1016/j.canlet.2021.06.007_bib54 article-title: Defining the role of mTOR in cancer publication-title: Canc. Cell doi: 10.1016/j.ccr.2007.05.008 – volume: 15 start-page: 943 year: 2019 ident: 10.1016/j.canlet.2021.06.007_bib18 article-title: KEYNOTE-585: phase III study of perioperative chemotherapy with or without pembrolizumab for gastric cancer publication-title: Future Oncol. doi: 10.2217/fon-2018-0581 – volume: 574 start-page: 45 year: 2019 ident: 10.1016/j.canlet.2021.06.007_bib15 article-title: Harnessing innate immunity in cancer therapy publication-title: Nature doi: 10.1038/s41586-019-1593-5 |
| SSID | ssj0005475 |
| Score | 2.6256297 |
| Snippet | Tumors evade immune surveillance by expressing Programmed Death-Ligand 1 (PD-L1), subsequently inhibiting CD8+ cytotoxic T lymphocyte function. Response of... Tumors evade immune surveillance by expressing Programmed Death-Ligand 1 (PD-L1), subsequently inhibiting CD8 cytotoxic T lymphocyte function. Response of... |
| SourceID | pubmedcentral proquest pubmed crossref elsevier |
| SourceType | Open Access Repository Aggregation Database Index Database Enrichment Source Publisher |
| StartPage | 59 |
| SubjectTerms | 1-Phosphatidylinositol 3-kinase AKT protein Apoptosis Autografts B7-H1 Antigen - genetics Cancer therapies CD8 antigen CD8-Positive T-Lymphocytes - metabolism Cell death Cells, Cultured Chemotherapy Cytokines Cytotoxic T lymphocytes Cytotoxicity Dendritic cells Epithelium Fatalities Gastric cancer Gene regulation Growth factors Hedgehog protein Hedgehog Proteins - genetics Helicobacter pylori - pathogenicity Human subjects Humans Immunomodulation Immunosurveillance Immunotherapy Immunotherapy - methods Ligands Lymphocytes Lymphocytes T Metastases Monoclonal antibodies Myeloid derived suppressor cells Organoids Organoids - metabolism PD-1 protein PD-L1 protein Rapamycin Regulation Signal transduction Signal Transduction - genetics Sonic hedgehog Stomach Neoplasms - genetics Stomach Neoplasms - microbiology T-Lymphocytes, Cytotoxic - metabolism Targeted cancer therapy TOR protein TOR Serine-Threonine Kinases - genetics Transcription Transcription, Genetic - genetics Transplantation Tumor microenvironment Tumor Microenvironment - genetics Tumor necrosis factor-TNF Tumors Zinc Finger Protein GLI1 - genetics |
| Title | Hedgehog transcriptional effector GLI mediates mTOR-Induced PD-L1 expression in gastric cancer organoids |
| URI | https://www.clinicalkey.com/#!/content/1-s2.0-S0304383521002925 https://dx.doi.org/10.1016/j.canlet.2021.06.007 https://www.ncbi.nlm.nih.gov/pubmed/34126195 https://www.proquest.com/docview/2558083195 https://www.proquest.com/docview/2541321482 https://pubmed.ncbi.nlm.nih.gov/PMC8606306 |
| Volume | 518 |
| hasFullText | 1 |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV3db9QwDLemISFeEN8cjClIvIZrm7RpH6eNcYNtINikvUWXNNkVQTvdbhJP_O2z07TaAdIQj21tKXEc22nsnwHeSINKktFOS9EESuUTbmoneJravHa-NDb8cDs6Lman8sNZfrYBu0MtDKVVRtvf2_RgreObaZTm9KJppl_pUk9QAEEoolVGheZSKtLyt79upHnIALZLxJyoh_K5kOOFo0fp4CkxSwOKJzWV_bt7-jP8_D2L8oZb2n8A92M8yXb6IT-EDdc-grtH8cb8MSxm9MNs0Z2zFXmlwUYgS5_J0S3Z-8MDFgpIMOpkP04-feHUzwMlwz7v8cOUuZ8xWbZlTcvO59TpwzJL6rJkoStU19SXT-B0_93J7ozH7grc5lKueJ1IhfKaO1tltfEEtFeUwpamks4WziTCe4Lns9YUykpRzH0lhbO1LercSC-ewmbbte45MCcFEojEK6ekEaLCF5l1MjGpz8vaTUAMQtU2Qo9TB4zvesgx-6b7pdC0FDqk2qkJ8JHroofeuIU-H9ZLD2WlaAg1-oZb-NTIt6Z6_8C5NaiFjlv_UuMZraT2bVU-gdfjZ9y0dBMzb113RTQYO2QEwTqBZ70WjVPEsIJOtcit1vRrJCBA8PUvbbMIwOBlQQhqxYv_ntBLuEdP5JvTZAs2V8sr9wqDrpXZDrtqG-7sHHycHV8DdkgtbA |
| linkProvider | Elsevier |
| linkToHtml | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwtV1Lb9QwEB6VVoJeUHl2oYCR4Bg2iZ3XgQOitLt0tyDYSr2ZtWN3gyCpdrcCLvyp_kFmnIe6gFSE1GvsiZKZ8Xhsf_4G4JlQ6CQhjbQAQ6BIrO-p3HAvCHSUG5sq7Tbcxofx4Ei8PY6O1-C8vQtDsMom9tcx3UXr5km_0Wb_tCj6H-lQj1MCQSyiWdgiKw_Mj2-4blu8HO6ikZ-H4d6byeuB15QW8HQkxNLLfZEIkUyNzsJcWWKZi1OuU5UJo2OjfG4tcdNpreJECx5PbSa40bmO80gJy_G912BDYLigsgkvfl7AlQjH7ktf59Hntff1HKgM1YXmwGVpGDjaUKpi-_f58M9893fY5oV5cG8LbjYJLHtV6-gWrJnyNlwfN0f0d2A2oB26WXXCljQNtkEJRWroSDVn-6MhczdWMM1lXyfvPnhUQARNwd7veqOAme8NOrdkRclOplRaRDNN_jlnrgxVVeSLu3B0JTq_B-tlVZptYEZw7MB9m5hEKM4zfBBqI3wV2CjNTQ94q1SpG65zKrnxRbagts-yNoUkU0iH7Ut64HVSpzXXxyX9o9Zesr3HipFX4mR0iVzSya34-j9I7rRuIZtYs5C4KEypXlwW9eBp14xRgo5-pqWpzqgPJishcb724H7tRd0vYh5Dy2iUTlb8q-tADOSrLWUxc0zkaUyUbfGD__6hJ3BjMBmP5Gh4ePAQNqmFEoPA34H15fzMPMKMb6keuxHG4NNVD-lf15hqcg |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Hedgehog+transcriptional+effector+GLI+mediates+mTOR-Induced+PD-L1+expression+in+gastric+cancer+organoids&rft.jtitle=Cancer+letters&rft.au=Koh%2C+Vivien&rft.au=Chakrabarti%2C+Jayati&rft.au=Torvund%2C+Meaghan&rft.au=Steele%2C+Nina&rft.date=2021-10-10&rft.pub=Elsevier+B.V&rft.issn=0304-3835&rft.volume=518&rft.spage=59&rft.epage=71&rft_id=info:doi/10.1016%2Fj.canlet.2021.06.007&rft.externalDocID=S0304383521002925 |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=0304-3835&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=0304-3835&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=0304-3835&client=summon |