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Targeting the loss of cGAS/STING signaling in cancer
The cGAS/STING pathway provides a key host defense mechanism by detecting the accumulation of cytoplasmic double‐stranded DNA (dsDNA) and mediating innate and adaptive immune signaling. In addition to detecting pathogen‐derived dsDNA, cGAS senses intrinsic dsDNA, such as those associated with defect...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10551601/ https://www.ncbi.nlm.nih.gov/pubmed/37475576 http://dx.doi.org/10.1111/cas.15913 |
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author | Sasaki, Nobunari Homme, Mizuki Kitajima, Shunsuke |
author_facet | Sasaki, Nobunari Homme, Mizuki Kitajima, Shunsuke |
author_sort | Sasaki, Nobunari |
collection | PubMed |
description | The cGAS/STING pathway provides a key host defense mechanism by detecting the accumulation of cytoplasmic double‐stranded DNA (dsDNA) and mediating innate and adaptive immune signaling. In addition to detecting pathogen‐derived dsDNA, cGAS senses intrinsic dsDNA, such as those associated with defective cell cycle progression and mitophagy that has leaked from the nucleus or mitochondria, and subsequently evokes host immunity to eliminate pathogenic cells. In cancer cells, dysregulation of DNA repair and cell cycle caused at the DNA replication checkpoint and spindle assembly checkpoint results in aberrant cytoplasmic dsDNA accumulation, stimulating anti‐tumor immunity. Therefore, the suppression of cGAS/STING signaling is beneficial for survival and frequently observed in cancer cells as a way to evade detection by the immune system, and is likely to be related to immune checkpoint blockade (ICB) resistance. Indeed, the mechanisms of ICB resistance overlap with those acquired in cancers during immunoediting to evade immune surveillance. This review highlights the current understanding of cGAS/STING suppression in cancer cells and discusses how to establish effective strategies to regenerate effective anti‐tumor immunity through reactivation of the cGAS/STING pathway. |
format | Online Article Text |
id | pubmed-10551601 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-105516012023-10-06 Targeting the loss of cGAS/STING signaling in cancer Sasaki, Nobunari Homme, Mizuki Kitajima, Shunsuke Cancer Sci Review Articles The cGAS/STING pathway provides a key host defense mechanism by detecting the accumulation of cytoplasmic double‐stranded DNA (dsDNA) and mediating innate and adaptive immune signaling. In addition to detecting pathogen‐derived dsDNA, cGAS senses intrinsic dsDNA, such as those associated with defective cell cycle progression and mitophagy that has leaked from the nucleus or mitochondria, and subsequently evokes host immunity to eliminate pathogenic cells. In cancer cells, dysregulation of DNA repair and cell cycle caused at the DNA replication checkpoint and spindle assembly checkpoint results in aberrant cytoplasmic dsDNA accumulation, stimulating anti‐tumor immunity. Therefore, the suppression of cGAS/STING signaling is beneficial for survival and frequently observed in cancer cells as a way to evade detection by the immune system, and is likely to be related to immune checkpoint blockade (ICB) resistance. Indeed, the mechanisms of ICB resistance overlap with those acquired in cancers during immunoediting to evade immune surveillance. This review highlights the current understanding of cGAS/STING suppression in cancer cells and discusses how to establish effective strategies to regenerate effective anti‐tumor immunity through reactivation of the cGAS/STING pathway. John Wiley and Sons Inc. 2023-07-20 /pmc/articles/PMC10551601/ /pubmed/37475576 http://dx.doi.org/10.1111/cas.15913 Text en © 2023 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Review Articles Sasaki, Nobunari Homme, Mizuki Kitajima, Shunsuke Targeting the loss of cGAS/STING signaling in cancer |
title | Targeting the loss of cGAS/STING signaling in cancer |
title_full | Targeting the loss of cGAS/STING signaling in cancer |
title_fullStr | Targeting the loss of cGAS/STING signaling in cancer |
title_full_unstemmed | Targeting the loss of cGAS/STING signaling in cancer |
title_short | Targeting the loss of cGAS/STING signaling in cancer |
title_sort | targeting the loss of cgas/sting signaling in cancer |
topic | Review Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10551601/ https://www.ncbi.nlm.nih.gov/pubmed/37475576 http://dx.doi.org/10.1111/cas.15913 |
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