Senescence rewires microenvironment sensing to facilitate anti-tumor immunity

Chen, Hsuan-An, Ho, Yu-Jui, Mezzadra, Riccardo, Adrover, Jose M, Smolkin, Ryan, Zhu, Changyu, Woess, Katharina, Bernstein, Nicholas, Schmitt, Georgia, Fong, Linda, Luan, Wei, Wuest, Alexandra, Tian, Sha, Li, Xiang, Broderick, Caroline, Hendrickson, Ronald C, Egeblad, Mikala, Chen, Zhenghao, Alonso-Curbelo, Direna, Lowe, Scott W (October 2022) Senescence rewires microenvironment sensing to facilitate anti-tumor immunity. Cancer Discovery. CD-22. ISSN 2159-8274

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URL: https://www.ncbi.nlm.nih.gov/pubmed/36302222
DOI: 10.1158/2159-8290.CD-22-0528

Abstract

Cellular senescence involves a stable cell cycle arrest coupled to a secretory program that, in some instances, stimulates the immune clearance of senescent cells. Using an immune competent liver cancer model in which senescence triggers CD8 T cell-mediated tumor rejection, we show that senescence also remodels the cell surface proteome to alter how tumor cells sense environmental factors, as exemplified by Type II interferon (IFN-y). Compared to proliferating cells, senescent cells upregulate the IFN-y receptor, become hypersensitized to microenvironmental IFN-y, and more robustly induce the antigen presenting machinery--effects also recapitulated in human tumor cells undergoing therapy-induced senescence. Disruption of IFN-y sensing in senescent cells blunts their immune-mediated clearance without disabling the senescence state or its characteristic secretory program. Our results demonstrate that senescent cells have an enhanced ability to both send and receive environmental signals, and imply that each process is required for their effective immune surveillance.

Item Type: Paper
Subjects: diseases & disorders > cancer
organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > cell cycle
organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > senescence
CSHL Authors:
Communities: CSHL labs > Egeblad lab
CSHL labs > Lowe lab
SWORD Depositor: CSHL Elements
Depositing User: CSHL Elements
Date: 27 October 2022
Date Deposited: 08 Nov 2022 16:23
Last Modified: 08 Nov 2022 16:23
URI: https://repository.cshl.edu/id/eprint/40748

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