Hepatocellular Senescence: Immunosurveillance and Future Senescence-Induced Therapy in Hepatocellular Carcinoma
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. The lack of effective targeted drugs has become a challenge on treating HCC patients. Cellular senescence is closely linked to the occurrence, development, and therapy of tumor. Induction of cellular senesc...
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| Published in | Frontiers in oncology Vol. 10; p. 589908 |
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| Main Authors | , , , , , , |
| Format | Journal Article |
| Language | English |
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27.11.2020
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| Abstract | Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. The lack of effective targeted drugs has become a challenge on treating HCC patients. Cellular senescence is closely linked to the occurrence, development, and therapy of tumor. Induction of cellular senescence and further activation of immune surveillance provides a new strategy to develop HCC targeted drugs, that is, senescence-induced therapy for HCC. Precancerous hepatocytes or HCC cells can be induced into senescent cells, subsequently producing senescence-associated secretory phenotype (SASP) factors. SASP factors recruit and activate various types of immune cells, including T cells, NK cells, macrophages, and their subtypes, which carry out the role of immune surveillance and elimination of senescent cells, ultimately preventing the occurrence of HCC or inhibiting the progression of HCC. Specific interventions in several checkpoints of senescence-mediated therapy will make positive contributions to suppress tumorigenesis and progression of HCC, for instance, by applying small molecular compounds to induce cellular senescence or selecting cytokines/chemokines to activate immunosurveillance, supplementing adoptive immunocytes to remove senescent cells, and screening chemical drugs to induce apoptosis of senescent cells or accelerate clearance of senescent cells. These interventional checkpoints become potential chemotherapeutic targets in senescence-induced therapy for HCC. In this review, we focus on the frontiers of senescence-induced therapy and discuss senescent characteristics of hepatocytes during hepatocarcinogenesis as well as the roles and mechanisms of senescent cell induction and clearance, and cellular senescence-related immunosurveillance during the formation and progression of HCC. |
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| AbstractList | Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. The lack of effective targeted drugs has become a challenge on treating HCC patients. Cellular senescence is closely linked to the occurrence, development, and therapy of tumor. Induction of cellular senescence and further activation of immune surveillance provides a new strategy to develop HCC targeted drugs, that is, senescence-induced therapy for HCC. Precancerous hepatocytes or HCC cells can be induced into senescent cells, subsequently producing senescence-associated secretory phenotype (SASP) factors. SASP factors recruit and activate various types of immune cells, including T cells, NK cells, macrophages, and their subtypes, which carry out the role of immune surveillance and elimination of senescent cells, ultimately preventing the occurrence of HCC or inhibiting the progression of HCC. Specific interventions in several checkpoints of senescence-mediated therapy will make positive contributions to suppress tumorigenesis and progression of HCC, for instance, by applying small molecular compounds to induce cellular senescence or selecting cytokines/chemokines to activate immunosurveillance, supplementing adoptive immunocytes to remove senescent cells, and screening chemical drugs to induce apoptosis of senescent cells or accelerate clearance of senescent cells. These interventional checkpoints become potential chemotherapeutic targets in senescence-induced therapy for HCC. In this review, we focus on the frontiers of senescence-induced therapy and discuss senescent characteristics of hepatocytes during hepatocarcinogenesis as well as the roles and mechanisms of senescent cell induction and clearance, and cellular senescence-related immunosurveillance during the formation and progression of HCC. Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. The lack of effective targeted drugs has become a challenge on treating HCC patients. Cellular senescence is closely linked to the occurrence, development, and therapy of tumor. Induction of cellular senescence and further activation of immune surveillance provides a new strategy to develop HCC targeted drugs, that is, senescence-induced therapy for HCC. Precancerous hepatocytes or HCC cells can be induced into senescent cells, subsequently producing senescence-associated secretory phenotype (SASP) factors. SASP factors recruit and activate various types of immune cells, including T cells, NK cells, macrophages, and their subtypes, which carry out the role of immune surveillance and elimination of senescent cells, ultimately preventing the occurrence of HCC or inhibiting the progression of HCC. Specific interventions in several checkpoints of senescence-mediated therapy will make positive contributions to suppress tumorigenesis and progression of HCC, for instance, by applying small molecular compounds to induce cellular senescence or selecting cytokines/chemokines to activate immunosurveillance, supplementing adoptive immunocytes to remove senescent cells, and screening chemical drugs to induce apoptosis of senescent cells or accelerate clearance of senescent cells. These interventional checkpoints become potential chemotherapeutic targets in senescence-induced therapy for HCC. In this review, we focus on the frontiers of senescence-induced therapy and discuss senescent characteristics of hepatocytes during hepatocarcinogenesis as well as the roles and mechanisms of senescent cell induction and clearance, and cellular senescence-related immunosurveillance during the formation and progression of HCC.Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. The lack of effective targeted drugs has become a challenge on treating HCC patients. Cellular senescence is closely linked to the occurrence, development, and therapy of tumor. Induction of cellular senescence and further activation of immune surveillance provides a new strategy to develop HCC targeted drugs, that is, senescence-induced therapy for HCC. Precancerous hepatocytes or HCC cells can be induced into senescent cells, subsequently producing senescence-associated secretory phenotype (SASP) factors. SASP factors recruit and activate various types of immune cells, including T cells, NK cells, macrophages, and their subtypes, which carry out the role of immune surveillance and elimination of senescent cells, ultimately preventing the occurrence of HCC or inhibiting the progression of HCC. Specific interventions in several checkpoints of senescence-mediated therapy will make positive contributions to suppress tumorigenesis and progression of HCC, for instance, by applying small molecular compounds to induce cellular senescence or selecting cytokines/chemokines to activate immunosurveillance, supplementing adoptive immunocytes to remove senescent cells, and screening chemical drugs to induce apoptosis of senescent cells or accelerate clearance of senescent cells. These interventional checkpoints become potential chemotherapeutic targets in senescence-induced therapy for HCC. In this review, we focus on the frontiers of senescence-induced therapy and discuss senescent characteristics of hepatocytes during hepatocarcinogenesis as well as the roles and mechanisms of senescent cell induction and clearance, and cellular senescence-related immunosurveillance during the formation and progression of HCC. |
| Author | Tang, Qinghe Liu, Zhongmin Chen, Wenjian Liu, Peng Chen, Miaomiao Lu, Yanli He, Zhiying |
| AuthorAffiliation | 2 Shanghai Institute of Stem Cell Research and Clinical Translation , Shanghai , China 1 Institute for Regenerative Medicine, Shanghai East Hospital, School of Life Sciences and Technology, Tongji University , Shanghai , China 3 Department of Hepatobiliary and Pancreatic Surgery, Shanghai East Hospital, Tongji University , Shanghai , China |
| AuthorAffiliation_xml | – name: 1 Institute for Regenerative Medicine, Shanghai East Hospital, School of Life Sciences and Technology, Tongji University , Shanghai , China – name: 3 Department of Hepatobiliary and Pancreatic Surgery, Shanghai East Hospital, Tongji University , Shanghai , China – name: 2 Shanghai Institute of Stem Cell Research and Clinical Translation , Shanghai , China |
| Author_xml | – sequence: 1 givenname: Peng surname: Liu fullname: Liu, Peng – sequence: 2 givenname: Qinghe surname: Tang fullname: Tang, Qinghe – sequence: 3 givenname: Miaomiao surname: Chen fullname: Chen, Miaomiao – sequence: 4 givenname: Wenjian surname: Chen fullname: Chen, Wenjian – sequence: 5 givenname: Yanli surname: Lu fullname: Lu, Yanli – sequence: 6 givenname: Zhongmin surname: Liu fullname: Liu, Zhongmin – sequence: 7 givenname: Zhiying surname: He fullname: He, Zhiying |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/33330071$$D View this record in MEDLINE/PubMed |
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| Keywords | hepatocellular senescence senescence-induced therapy cellular senescence senescence-associated secretory phenotype immunosurveillance hepatocellular carcinoma |
| Language | English |
| License | Copyright © 2020 Liu, Tang, Chen, Chen, Lu, Liu and He. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
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| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 ObjectType-Review-3 content type line 23 Edited by: Weijia Fang, Zhejiang University, China These authors have contributed equally to this work This article was submitted to Gastrointestinal Cancers, a section of the journal Frontiers in Oncology Reviewed by: Kazumichi Kawakubo, Hokkaido University Hospital, Japan; Qingyuan Yang, Massachusetts General Hospital and Harvard Medical School, United States |
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| Title | Hepatocellular Senescence: Immunosurveillance and Future Senescence-Induced Therapy in Hepatocellular Carcinoma |
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