P2X7 Receptor Activity Limits Accumulation of T Cells within Tumors
Extracellular ATP (eATP) is a signaling molecule that variably affects all cells of the immune system either directly or after hydrolysis to adenosine. Although eATP is virtually absent in the interstitium of normal tissues, it can be present in the hundreds of micromolar range in tumors, a concentr...
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| Published in | Cancer research (Chicago, Ill.) Vol. 80; no. 18; pp. 3906 - 3919 |
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| Main Authors | , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
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United States
15.09.2020
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| Subjects | |
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| Abstract | Extracellular ATP (eATP) is a signaling molecule that variably affects all cells of the immune system either directly or after hydrolysis to adenosine. Although eATP is virtually absent in the interstitium of normal tissues, it can be present in the hundreds of micromolar range in tumors, a concentration compatible with activation of the ATP-gated ionotropic P2X7 receptor. Here, we show that P2X7 activity in tumor-infiltrating lymphocytes (TIL) induces cellular senescence and limits tumor suppression. P2X7 stimulation affected cell cycling of effector T cells and resulted in generation of mitochondrial reactive oxygen species and p38 MAPK-dependent upregulation of cyclin-dependent kinase inhibitor 1A (Cdkn1a, encoding for p21Waf1/Cip1). Lack of P2X7 promoted a transcriptional signature that correlated with enhanced cytotoxic T-cell response in human solid tumors. In mice, transfer of tumor-specific T cells with deletion of P2rx7 significantly reduced tumor growth and extended survival. Collectively, these findings uncover a purinergic checkpoint that can be targeted to improve the efficacy of cancer immunotherapy strategies. |
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| AbstractList | Extracellular ATP (eATP) is a signaling molecule that variably affects all cells of the immune system either directly or after hydrolysis to adenosine. Although eATP is virtually absent in the interstitium of normal tissues, it can be present in the hundreds of micromolar range in tumors, a concentration compatible with activation of the ATP-gated ionotropic P2X7 receptor. Here, we show that P2X7 activity in tumor-infiltrating lymphocytes (TIL) induces cellular senescence and limits tumor suppression. P2X7 stimulation affected cell cycling of effector T cells and resulted in generation of mitochondrial reactive oxygen species and p38 MAPK-dependent upregulation of cyclin-dependent kinase inhibitor 1A (Cdkn1a, encoding for p21Waf1/Cip1). Lack of P2X7 promoted a transcriptional signature that correlated with enhanced cytotoxic T-cell response in human solid tumors. In mice, transfer of tumor-specific T cells with deletion of P2rx7 significantly reduced tumor growth and extended survival. Collectively, these findings uncover a purinergic checkpoint that can be targeted to improve the efficacy of cancer immunotherapy strategies. SIGNIFICANCE: These findings suggest that the purinergic checkpoint P2X7 may be targeted to enhance T-cell-mediated cancer immunotherapy and improve T effector cell accumulation in the tumor microenvironment. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/80/18/3906/F1.large.jpg.Extracellular ATP (eATP) is a signaling molecule that variably affects all cells of the immune system either directly or after hydrolysis to adenosine. Although eATP is virtually absent in the interstitium of normal tissues, it can be present in the hundreds of micromolar range in tumors, a concentration compatible with activation of the ATP-gated ionotropic P2X7 receptor. Here, we show that P2X7 activity in tumor-infiltrating lymphocytes (TIL) induces cellular senescence and limits tumor suppression. P2X7 stimulation affected cell cycling of effector T cells and resulted in generation of mitochondrial reactive oxygen species and p38 MAPK-dependent upregulation of cyclin-dependent kinase inhibitor 1A (Cdkn1a, encoding for p21Waf1/Cip1). Lack of P2X7 promoted a transcriptional signature that correlated with enhanced cytotoxic T-cell response in human solid tumors. In mice, transfer of tumor-specific T cells with deletion of P2rx7 significantly reduced tumor growth and extended survival. Collectively, these findings uncover a purinergic checkpoint that can be targeted to improve the efficacy of cancer immunotherapy strategies. SIGNIFICANCE: These findings suggest that the purinergic checkpoint P2X7 may be targeted to enhance T-cell-mediated cancer immunotherapy and improve T effector cell accumulation in the tumor microenvironment. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/80/18/3906/F1.large.jpg. Extracellular ATP (eATP) is a signaling molecule that variably affects all cells of the immune system either directly or after hydrolysis to adenosine. Although eATP is virtually absent in the interstitium of normal tissues, it can be present in the hundreds of micromolar range in tumors, a concentration compatible with activation of the ATP-gated ionotropic P2X7 receptor. Here, we show that P2X7 activity in tumor-infiltrating lymphocytes (TIL) induces cellular senescence and limits tumor suppression. P2X7 stimulation affected cell cycling of effector T cells and resulted in generation of mitochondrial reactive oxygen species and p38 MAPK-dependent upregulation of cyclin-dependent kinase inhibitor 1A ( , encoding for p21 ). Lack of P2X7 promoted a transcriptional signature that correlated with enhanced cytotoxic T-cell response in human solid tumors. In mice, transfer of tumor-specific T cells with deletion of significantly reduced tumor growth and extended survival. Collectively, these findings uncover a purinergic checkpoint that can be targeted to improve the efficacy of cancer immunotherapy strategies. SIGNIFICANCE: These findings suggest that the purinergic checkpoint P2X7 may be targeted to enhance T-cell-mediated cancer immunotherapy and improve T effector cell accumulation in the tumor microenvironment. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/80/18/3906/F1.large.jpg. Extracellular adenosine triphosphate (eATP) is a signaling molecule which variably affects all cells of the immune system either directly or after hydrolysis to adenosine. Although eATP is virtually absent in the interstitium of normal tissues, it can be present in the hundreds of micromolar range in tumors, a concentration compatible with activation of the ATP-gated ionotropic P2X7 receptor. Here we show that P2X7 activity in tumor-infiltrating T cells (TILs) induces cellular senescence and limits tumor suppression. P2X7 stimulation affected cell cycling of effector T cells and resulted in generation of mitochondrial reactive oxygen species (ROS) and p38 MAPK-dependent upregulation of cyclin-dependent kinase inhibitor 1A ( Cdkn1a , encoding for p21 Waf1/Cip1 ). Lack of P2X7 promoted a transcriptional signature that correlated with enhanced cytotoxic T cell response in human solid tumors. In mice, transfer of tumor specific T cells with deletion of P2rx7 significantly reduced tumor growth and extended survival. Collectively, these findings uncover a purinergic checkpoint that can be targeted to improve the efficacy of cancer immunotherapy strategies. Extracellular ATP (eATP) is a signaling molecule that variably affects all cells of the immune system either directly or after hydrolysis to adenosine. Although eATP is virtually absent in the interstitium of normal tissues, it can be present in the hundreds of micromolar range in tumors, a concentration compatible with activation of the ATP-gated ionotropic P2X7 receptor. Here, we show that P2X7 activity in tumor-infiltrating lymphocytes (TIL) induces cellular senescence and limits tumor suppression. P2X7 stimulation affected cell cycling of effector T cells and resulted in generation of mitochondrial reactive oxygen species and p38 MAPK-dependent upregulation of cyclin-dependent kinase inhibitor 1A (Cdkn1a, encoding for p21Waf1/Cip1). Lack of P2X7 promoted a transcriptional signature that correlated with enhanced cytotoxic T-cell response in human solid tumors. In mice, transfer of tumor-specific T cells with deletion of P2rx7 significantly reduced tumor growth and extended survival. Collectively, these findings uncover a purinergic checkpoint that can be targeted to improve the efficacy of cancer immunotherapy strategies. |
| Author | Grassi, Fabio Rottoli, Elsa Di Virgilio, Francesco Mazza, Emilia Maria Cristina Proietti, Michele Civanelli, Elisa Catapano, Alberico L. Tagliafico, Enrico De Ponte Conti, Benedetta Perruzza, Lisa Bicciato, Silvio Baragetti, Andrea Rezzonico-Jost, Tanja Tenedini, Elena Romagnani, Andrea Falzoni, Simonetta Norata, Giuseppe Danilo Perotti, Michela |
| AuthorAffiliation | 1 Institute for Research in Biomedicine, Faculty of Biomedical Sciences, Università della Svizzera Italiana, 6500 Bellinzona, Switzerland 2 Department of Medical Biotechnology and Translational Medicine, University of Milan, 20129 Milan, Italy 4 Institute for Microbiology, ETH Zürich, 8093 Zürich, Switzerland 8 Department of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology, University of Ferrara, 44121 Ferrara, Italy 3 Department of Life Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy 5 Department of Excellence in Pharmacological and Biomolecular Sciences, University of Milan, 20133 Milan, Italy 6 IRCSS Multimedica, 20138 Milan, Italy 9 Istituto Nazionale Genetica Molecolare “Romeo ed Enrica Invernizzi”, 20122 Milan, Italy 7 Department of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio Emilia, 41125 Modena, Italy |
| AuthorAffiliation_xml | – name: 8 Department of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology, University of Ferrara, 44121 Ferrara, Italy – name: 7 Department of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio Emilia, 41125 Modena, Italy – name: 2 Department of Medical Biotechnology and Translational Medicine, University of Milan, 20129 Milan, Italy – name: 4 Institute for Microbiology, ETH Zürich, 8093 Zürich, Switzerland – name: 9 Istituto Nazionale Genetica Molecolare “Romeo ed Enrica Invernizzi”, 20122 Milan, Italy – name: 5 Department of Excellence in Pharmacological and Biomolecular Sciences, University of Milan, 20133 Milan, Italy – name: 1 Institute for Research in Biomedicine, Faculty of Biomedical Sciences, Università della Svizzera Italiana, 6500 Bellinzona, Switzerland – name: 3 Department of Life Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy – name: 6 IRCSS Multimedica, 20138 Milan, Italy |
| Author_xml | – sequence: 1 givenname: Andrea surname: Romagnani fullname: Romagnani, Andrea – sequence: 2 givenname: Elsa surname: Rottoli fullname: Rottoli, Elsa – sequence: 3 givenname: Emilia Maria Cristina surname: Mazza fullname: Mazza, Emilia Maria Cristina – sequence: 4 givenname: Tanja surname: Rezzonico-Jost fullname: Rezzonico-Jost, Tanja – sequence: 5 givenname: Benedetta surname: De Ponte Conti fullname: De Ponte Conti, Benedetta – sequence: 6 givenname: Michele surname: Proietti fullname: Proietti, Michele – sequence: 7 givenname: Michela surname: Perotti fullname: Perotti, Michela – sequence: 8 givenname: Elisa surname: Civanelli fullname: Civanelli, Elisa – sequence: 9 givenname: Lisa surname: Perruzza fullname: Perruzza, Lisa – sequence: 10 givenname: Alberico L. orcidid: 0000-0002-7593-2094 surname: Catapano fullname: Catapano, Alberico L. – sequence: 11 givenname: Andrea surname: Baragetti fullname: Baragetti, Andrea – sequence: 12 givenname: Elena surname: Tenedini fullname: Tenedini, Elena – sequence: 13 givenname: Enrico surname: Tagliafico fullname: Tagliafico, Enrico – sequence: 14 givenname: Simonetta surname: Falzoni fullname: Falzoni, Simonetta – sequence: 15 givenname: Francesco orcidid: 0000-0003-3566-1362 surname: Di Virgilio fullname: Di Virgilio, Francesco – sequence: 16 givenname: Giuseppe Danilo surname: Norata fullname: Norata, Giuseppe Danilo – sequence: 17 givenname: Silvio orcidid: 0000-0002-1944-7078 surname: Bicciato fullname: Bicciato, Silvio – sequence: 18 givenname: Fabio surname: Grassi fullname: Grassi, Fabio |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/32699136$$D View this record in MEDLINE/PubMed |
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| Cites_doi | 10.1084/jem.20171976 10.4049/jimmunol.179.1.186 10.1016/j.cell.2017.08.018 10.4049/jimmunol.1101582 10.1038/s41591-018-0266-5 10.1002/9780470032244.ch4 10.1158/1078-0432.CCR-13-2627 10.1038/nature19364 10.1073/pnas.1319784110 10.1074/jbc.273.10.5858 10.1016/j.cell.2018.11.043 10.1096/fj.09-150862 10.1016/j.bpj.2013.05.006 10.1182/blood-2010-04-277707 10.1111/joim.12081 10.1016/j.coph.2016.06.009 10.1038/s41586-019-0985-x 10.1093/biostatistics/4.2.249 10.1038/s41467-018-05072-0 10.1016/j.immuni.2013.07.005 10.1038/s41590-019-0312-6 10.1016/j.cell.2015.08.016 10.1007/978-1-4939-9717-6_13 10.1016/j.cell.2015.08.012 10.1016/j.immuni.2014.10.010 10.1126/scitranslmed.aaa0984 10.1056/NEJM198812223192527 10.1016/j.molmed.2003.11.003 10.1038/s41586-018-0282-0 10.1111/j.1600-065X.2008.00602.x 10.1038/s41586-018-0130-2 10.1038/nprot.2007.297 10.1038/s41388-019-0684-y 10.1126/sciimmunol.aau1022 10.1371/journal.pone.0002599 10.1073/pnas.091062498 10.1161/01.STR.0000221803.16897.22 10.1073/pnas.1619336114 10.1200/JCO.2014.58.0225 10.1016/j.mad.2017.07.007 10.1038/s41591-018-0078-7 10.1038/s41467-017-02689-5 10.1016/j.cell.2015.03.045 10.1038/nri1685 10.1016/j.molcel.2014.05.007 10.1016/j.it.2019.02.002 10.1038/s41577-018-0044-0 10.1111/imr.12571 10.1158/0008-5472.CAN-14-1259 10.1126/scisignal.1160583 10.1056/NEJMra1706169 10.1523/JNEUROSCI.2235-12.2013 10.1038/ni.3775 10.1016/j.it.2016.09.002 10.1210/jc.2014-4160 10.4049/jimmunol.1201510 10.1158/2159-8290.CD-19-0541 |
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| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Present address: F. Hoffmann-La Roche Ltd, 4070 Basel, Switzerland (A.R.); Laboratory of Translational Immunology, Humanitas Clinical and Research Center, 20089 Rozzano, Milan, Italy (E.M.C.M.); CCI-Center for Chronic Immunodeficiency, Universitätsklinikum Freiburg, 79106 Freiburg, Germany (M.P.). |
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| References | Khadra (2022061706330020400_bib17) 2013; 104 Ho (2022061706330020400_bib5) 2015; 162 Proietti (2022061706330020400_bib50) 2014; 41 De Marchi (2022061706330020400_bib20) 2020; 2041 Ahmed (2022061706330020400_bib46) 2015; 33 Rosenberg (2022061706330020400_bib1) 1988; 319 Li (2022061706330020400_bib41) 2019; 176 Klein Geltink (2022061706330020400_bib19) 2017; 171 Woehrle (2022061706330020400_bib27) 2010; 116 Savas (2022061706330020400_bib31) 2018; 24 Stokes (2022061706330020400_bib39) 2010; 24 Topalian (2022061706330020400_bib3) 2015; 161 Rogakou (2022061706330020400_bib34) 1998; 273 Burnstock (2022061706330020400_bib15) 2006; 276 Ganesan (2022061706330020400_bib30) 2017; 18 Todd (2022061706330020400_bib38) 2015; 100 Stark (2022061706330020400_bib52) 2018; 3 Sitkovsky (2022061706330020400_bib8) 2005; 5 Moon (2022061706330020400_bib47) 2014; 20 O'Rourke (2022061706330020400_bib48) 2017; 9 Adinolfi (2022061706330020400_bib57) 2015; 75 Duhen (2022061706330020400_bib29) 2018; 9 Norata (2022061706330020400_bib37) 2006; 37 June (2022061706330020400_bib45) 2018; 379 Hatfield (2022061706330020400_bib14) 2016; 29 Paucek (2022061706330020400_bib2) 2019; 40 Li (2022061706330020400_bib56) 2019; 9 Simoni (2022061706330020400_bib44) 2018; 557 Tusher (2022061706330020400_bib22) 2001; 98 Irizarry (2022061706330020400_bib21) 2003; 4 Schenk (2022061706330020400_bib26) 2008; 1 Adriouch (2022061706330020400_bib24) 2007; 179 Kepp (2022061706330020400_bib12) 2017; 280 Browne (2022061706330020400_bib16) 2013; 33 Munn (2022061706330020400_bib6) 2004; 10 Vono (2022061706330020400_bib11) 2013; 110 Liu (2022061706330020400_bib55) 2018; 9 Frascoli (2022061706330020400_bib18) 2012; 189 Scheper (2022061706330020400_bib43) 2019; 25 Borges da Silva (2022061706330020400_bib53) 2018; 559 Borst (2022061706330020400_bib25) 2018; 18 Krenning (2022061706330020400_bib32) 2014; 55 Baragetti (2022061706330020400_bib36) 2013; 274 Soto (2022061706330020400_bib51) 2017; 114 Ott (2022061706330020400_bib54) 2018; 170 Chen (2022061706330020400_bib49) 2019; 567 Foster (2022061706330020400_bib33) 2013; 190 Marigo (2022061706330020400_bib7) 2008; 222 Miller (2022061706330020400_bib42) 2019; 20 Faliti (2022061706330020400_bib13) 2019; 216 Chang (2022061706330020400_bib4) 2015; 162 Akbar (2022061706330020400_bib35) 2016; 37 Eil (2022061706330020400_bib9) 2016; 537 Pellegatti (2022061706330020400_bib10) 2008; 3 Hawkins (2022061706330020400_bib28) 2007; 2 Motz (2022061706330020400_bib40) 2013; 39 De Marchi (2022061706330020400_bib23) 2019; 38 |
| References_xml | – volume: 216 start-page: 317 year: 2019 ident: 2022061706330020400_bib13 article-title: P2X7 receptor restrains pathogenic Tfh cell generation in systemic lupus erythematosus publication-title: J Exp Med doi: 10.1084/jem.20171976 – volume: 179 start-page: 186 year: 2007 ident: 2022061706330020400_bib24 article-title: NAD+ released during inflammation participates in T cell homeostasis by inducing ART2-mediated death of naive T cells in vivo publication-title: J Immunol doi: 10.4049/jimmunol.179.1.186 – volume: 171 start-page: 385 year: 2017 ident: 2022061706330020400_bib19 article-title: Mitochondrial priming by CD28 publication-title: Cell doi: 10.1016/j.cell.2017.08.018 – volume: 189 start-page: 174 year: 2012 ident: 2022061706330020400_bib18 article-title: Purinergic P2X7 receptor drives T cell lineage choice and shapes peripheral γδ cells publication-title: J Immunol doi: 10.4049/jimmunol.1101582 – volume: 25 start-page: 89 year: 2019 ident: 2022061706330020400_bib43 article-title: Low and variable tumor reactivity of the intratumoral TCR repertoire in human cancers publication-title: Nat Med doi: 10.1038/s41591-018-0266-5 – volume: 276 start-page: 26 year: 2006 ident: 2022061706330020400_bib15 article-title: Purinergic signalling–an overview publication-title: Novartis Found Symp doi: 10.1002/9780470032244.ch4 – volume: 20 start-page: 4262 year: 2014 ident: 2022061706330020400_bib47 article-title: Multifactorial T-cell hypofunction that is reversible can limit the efficacy of chimeric antigen receptor-transduced human T cells in solid tumors publication-title: Clin Cancer Res doi: 10.1158/1078-0432.CCR-13-2627 – volume: 537 start-page: 539 year: 2016 ident: 2022061706330020400_bib9 article-title: Ionic immune suppression within the tumour microenvironment limits T cell effector function publication-title: Nature doi: 10.1038/nature19364 – volume: 110 start-page: 21095 year: 2013 ident: 2022061706330020400_bib11 article-title: The adjuvant MF59 induces ATP release from muscle that potentiates response to vaccination publication-title: Proc Natl Acad Sci U S A doi: 10.1073/pnas.1319784110 – volume: 273 start-page: 5858 year: 1998 ident: 2022061706330020400_bib34 article-title: DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139 publication-title: J Biol Chem doi: 10.1074/jbc.273.10.5858 – volume: 176 start-page: 775 year: 2019 ident: 2022061706330020400_bib41 article-title: Dysfunctional CD8 T cells form a proliferative, dynamically regulated compartment within human melanoma publication-title: Cell doi: 10.1016/j.cell.2018.11.043 – volume: 24 start-page: 2916 year: 2010 ident: 2022061706330020400_bib39 article-title: Two haplotypes of the P2X(7) receptor containing the Ala-348 to Thr polymorphism exhibit a gain-of-function effect and enhanced interleukin-1beta secretion publication-title: FASEB J doi: 10.1096/fj.09-150862 – volume: 104 start-page: 2612 year: 2013 ident: 2022061706330020400_bib17 article-title: Dual gating mechanism and function of P2X7 receptor channels publication-title: Biophys J doi: 10.1016/j.bpj.2013.05.006 – volume: 116 start-page: 3475 year: 2010 ident: 2022061706330020400_bib27 article-title: Pannexin-1 hemichannel-mediated ATP release together with P2X1 and P2X4 receptors regulate T-cell activation at the immune synapse publication-title: Blood doi: 10.1182/blood-2010-04-277707 – volume: 274 start-page: 252 year: 2013 ident: 2022061706330020400_bib36 article-title: High density lipoprotein cholesterol levels are an independent predictor of the progression of chronic kidney disease publication-title: J Intern Med doi: 10.1111/joim.12081 – volume: 29 start-page: 90 year: 2016 ident: 2022061706330020400_bib14 article-title: A2A adenosine receptor antagonists to weaken the hypoxia-HIF-1alpha driven immunosuppression and improve immunotherapies of cancer publication-title: Curr Opin Pharmacol doi: 10.1016/j.coph.2016.06.009 – volume: 567 start-page: 530 year: 2019 ident: 2022061706330020400_bib49 article-title: NR4A transcription factors limit CAR T cell function in solid tumours publication-title: Nature doi: 10.1038/s41586-019-0985-x – volume: 4 start-page: 249 year: 2003 ident: 2022061706330020400_bib21 article-title: Exploration, normalization, and summaries of high density oligonucleotide array probe level data publication-title: Biostatistics doi: 10.1093/biostatistics/4.2.249 – volume: 9 start-page: 2724 year: 2018 ident: 2022061706330020400_bib29 article-title: Co-expression of CD39 and CD103 identifies tumor-reactive CD8 T cells in human solid tumors publication-title: Nat Commun doi: 10.1038/s41467-018-05072-0 – volume: 39 start-page: 61 year: 2013 ident: 2022061706330020400_bib40 article-title: Deciphering and reversing tumor immune suppression publication-title: Immunity doi: 10.1016/j.immuni.2013.07.005 – volume: 20 start-page: 326 year: 2019 ident: 2022061706330020400_bib42 article-title: Subsets of exhausted CD8(+) T cells differentially mediate tumor control and respond to checkpoint blockade publication-title: Nat Immunol doi: 10.1038/s41590-019-0312-6 – volume: 162 start-page: 1229 year: 2015 ident: 2022061706330020400_bib4 article-title: Metabolic competition in the tumor microenvironment is a driver of cancer progression publication-title: Cell doi: 10.1016/j.cell.2015.08.016 – volume: 2041 start-page: 183 year: 2020 ident: 2022061706330020400_bib20 article-title: Detection of extracellular ATP in the tumor microenvironment, using the pmeLUC biosensor publication-title: Methods Mol Biol doi: 10.1007/978-1-4939-9717-6_13 – volume: 162 start-page: 1217 year: 2015 ident: 2022061706330020400_bib5 article-title: Phosphoenolpyruvate is a metabolic checkpoint of anti-tumor T cell responses publication-title: Cell doi: 10.1016/j.cell.2015.08.012 – volume: 41 start-page: 789 year: 2014 ident: 2022061706330020400_bib50 article-title: ATP-gated ionotropic P2X7 receptor controls follicular T helper cell numbers in Peyer's patches to promote host-microbiota mutualism publication-title: Immunity doi: 10.1016/j.immuni.2014.10.010 – volume: 9 start-page: eaaa0984 year: 2017 ident: 2022061706330020400_bib48 article-title: A single dose of peripherally infused EGFRvIII-directed CAR T cells mediates antigen loss and induces adaptive resistance in patients with recurrent glioblastoma publication-title: Sci Transl Med doi: 10.1126/scitranslmed.aaa0984 – volume: 319 start-page: 1676 year: 1988 ident: 2022061706330020400_bib1 article-title: Use of tumor-infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma. a preliminary report publication-title: N Engl J Med doi: 10.1056/NEJM198812223192527 – volume: 10 start-page: 15 year: 2004 ident: 2022061706330020400_bib6 article-title: IDO and tolerance to tumors publication-title: Trends Mol Med doi: 10.1016/j.molmed.2003.11.003 – volume: 559 start-page: 264 year: 2018 ident: 2022061706330020400_bib53 article-title: The purinergic receptor P2RX7 directs metabolic fitness of long-lived memory CD8(+) T cells publication-title: Nature doi: 10.1038/s41586-018-0282-0 – volume: 222 start-page: 162 year: 2008 ident: 2022061706330020400_bib7 article-title: Tumor-induced tolerance and immune suppression by myeloid derived suppressor cells publication-title: Immunol Rev doi: 10.1111/j.1600-065X.2008.00602.x – volume: 557 start-page: 575 year: 2018 ident: 2022061706330020400_bib44 article-title: Bystander CD8(+) T cells are abundant and phenotypically distinct in human tumour infiltrates publication-title: Nature doi: 10.1038/s41586-018-0130-2 – volume: 2 start-page: 2057 year: 2007 ident: 2022061706330020400_bib28 article-title: Measuring lymphocyte proliferation, survival and differentiation using CFSE time-series data publication-title: Nat Protoc doi: 10.1038/nprot.2007.297 – volume: 38 start-page: 3636 year: 2019 ident: 2022061706330020400_bib23 article-title: The P2X7 receptor modulates immune cells infiltration, ectonucleotidases expression and extracellular ATP levels in the tumor microenvironment publication-title: Oncogene doi: 10.1038/s41388-019-0684-y – volume: 3 start-page: eaau1022 year: 2018 ident: 2022061706330020400_bib52 article-title: T RM maintenance is regulated by tissue damage via P2RX7 publication-title: Sci Immunol doi: 10.1126/sciimmunol.aau1022 – volume: 3 start-page: e2599 year: 2008 ident: 2022061706330020400_bib10 article-title: Increased level of extracellular ATP at tumor sites: in vivo imaging with plasma membrane luciferase publication-title: PLoS One doi: 10.1371/journal.pone.0002599 – volume: 98 start-page: 5116 year: 2001 ident: 2022061706330020400_bib22 article-title: Significance analysis of microarrays applied to the ionizing radiation response publication-title: Proc Natl Acad Sci U S A doi: 10.1073/pnas.091062498 – volume: 37 start-page: 1558 year: 2006 ident: 2022061706330020400_bib37 article-title: Effects of fractalkine receptor variants on common carotid artery intima-media thickness publication-title: Stroke doi: 10.1161/01.STR.0000221803.16897.22 – volume: 114 start-page: 5497 year: 2017 ident: 2022061706330020400_bib51 article-title: Microbiota promotes systemic T-cell survival through suppression of an apoptotic factor publication-title: Proc Natl Acad Sci U S A doi: 10.1073/pnas.1619336114 – volume: 33 start-page: 1688 year: 2015 ident: 2022061706330020400_bib46 article-title: Human epidermal growth factor receptor 2 (HER2)-specific chimeric antigen receptor-modified T cells for the immunotherapy of HER2-positive sarcoma publication-title: J Clin Oncol doi: 10.1200/JCO.2014.58.0225 – volume: 170 start-page: 72 year: 2018 ident: 2022061706330020400_bib54 article-title: SIPS as a model to study age-related changes in proteolysis and aggregate formation publication-title: Mech Ageing Dev doi: 10.1016/j.mad.2017.07.007 – volume: 24 start-page: 986 year: 2018 ident: 2022061706330020400_bib31 article-title: Single-cell profiling of breast cancer T cells reveals a tissue-resident memory subset associated with improved prognosis publication-title: Nat Med doi: 10.1038/s41591-018-0078-7 – volume: 9 start-page: 249 year: 2018 ident: 2022061706330020400_bib55 article-title: Regulatory T cells trigger effector T cell DNA damage and senescence caused by metabolic competition publication-title: Nat Commun doi: 10.1038/s41467-017-02689-5 – volume: 161 start-page: 185 year: 2015 ident: 2022061706330020400_bib3 article-title: Immunotherapy: the path to win the war on cancer? publication-title: Cell doi: 10.1016/j.cell.2015.03.045 – volume: 5 start-page: 712 year: 2005 ident: 2022061706330020400_bib8 article-title: Regulation of immune cells by local-tissue oxygen tension: HIF1 alpha and adenosine receptors publication-title: Nat Rev Immunol doi: 10.1038/nri1685 – volume: 55 start-page: 59 year: 2014 ident: 2022061706330020400_bib32 article-title: Transient activation of p53 in G2 phase is sufficient to induce senescence publication-title: Mol Cell doi: 10.1016/j.molcel.2014.05.007 – volume: 40 start-page: 292 year: 2019 ident: 2022061706330020400_bib2 article-title: The cellular immunotherapy revolution: arming the immune system for precision therapy publication-title: Trends Immunol doi: 10.1016/j.it.2019.02.002 – volume: 18 start-page: 635 year: 2018 ident: 2022061706330020400_bib25 article-title: CD4+ T cell help in cancer immunology and immunotherapy publication-title: Nat Rev Immunol doi: 10.1038/s41577-018-0044-0 – volume: 280 start-page: 83 year: 2017 ident: 2022061706330020400_bib12 article-title: Extracellular nucleosides and nucleotides as immunomodulators publication-title: Immunol Rev doi: 10.1111/imr.12571 – volume: 75 start-page: 635 year: 2015 ident: 2022061706330020400_bib57 article-title: Accelerated tumor progression in mice lacking the ATP receptor P2X7 publication-title: Cancer Res doi: 10.1158/0008-5472.CAN-14-1259 – volume: 1 start-page: ra6 year: 2008 ident: 2022061706330020400_bib26 article-title: Purinergic control of T cell activation by ATP released through pannexin-1 hemichannels publication-title: Sci Signal doi: 10.1126/scisignal.1160583 – volume: 379 start-page: 64 year: 2018 ident: 2022061706330020400_bib45 article-title: Chimeric antigen receptor therapy publication-title: N Engl J Med doi: 10.1056/NEJMra1706169 – volume: 33 start-page: 3557 year: 2013 ident: 2022061706330020400_bib16 article-title: P2X7 receptor channels allow direct permeation of nanometer-sized dyes publication-title: J Neurosci doi: 10.1523/JNEUROSCI.2235-12.2013 – volume: 18 start-page: 940 year: 2017 ident: 2022061706330020400_bib30 article-title: Tissue-resident memory features are linked to the magnitude of cytotoxic T cell responses in human lung cancer publication-title: Nat Immunol doi: 10.1038/ni.3775 – volume: 37 start-page: 866 year: 2016 ident: 2022061706330020400_bib35 article-title: Senescence of T lymphocytes: implications for enhancing human immunity publication-title: Trends Immunol doi: 10.1016/j.it.2016.09.002 – volume: 100 start-page: E688 year: 2015 ident: 2022061706330020400_bib38 article-title: Variation in glucose homeostasis traits associated with P2RX7 polymorphisms in mice and humans publication-title: J Clin Endocrinol Metab doi: 10.1210/jc.2014-4160 – volume: 190 start-page: 1551 year: 2013 ident: 2022061706330020400_bib33 article-title: Mitochondrial superoxide generation enhances P2X7R-mediated loss of cell surface CD62L on naive human CD4+ T lymphocytes publication-title: J Immunol doi: 10.4049/jimmunol.1201510 – volume: 9 start-page: 1754 year: 2019 ident: 2022061706330020400_bib56 article-title: Targeting CD39 in cancer reveals an extracellular ATP- and inflammasome-driven tumor immunity publication-title: Cancer Discov doi: 10.1158/2159-8290.CD-19-0541 |
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| Snippet | Extracellular ATP (eATP) is a signaling molecule that variably affects all cells of the immune system either directly or after hydrolysis to adenosine.... Extracellular adenosine triphosphate (eATP) is a signaling molecule which variably affects all cells of the immune system either directly or after hydrolysis... |
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| SubjectTerms | Adenosine Triphosphate - metabolism Animals CD4-Positive T-Lymphocytes - immunology CD8-Positive T-Lymphocytes - immunology Cell Cycle Cell Line, Tumor Cell Migration Inhibition Cellular Senescence - immunology Cyclin-Dependent Kinase Inhibitor p21 - metabolism Flow Cytometry - methods Gene Expression Profiling Humans Immune Checkpoint Inhibitors - therapeutic use Immunotherapy, Adoptive - methods Lymphocytes, Tumor-Infiltrating - immunology Lymphocytes, Tumor-Infiltrating - metabolism Melanoma, Experimental - immunology Melanoma, Experimental - pathology Melanoma, Experimental - therapy Mice Mice, Inbred C57BL Mitochondria - metabolism Neoplasm Transplantation Purinergic P2X Receptor Antagonists Reactive Oxygen Species - metabolism Receptors, Purinergic P2X7 - deficiency Receptors, Purinergic P2X7 - metabolism T-Lymphocytes, Cytotoxic - immunology Transcription, Genetic Tumor Microenvironment - immunology Up-Regulation |
| Title | P2X7 Receptor Activity Limits Accumulation of T Cells within Tumors |
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