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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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 diseases & disorders diseases & disorders > neoplasms 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 organs, tissues, organelles, cell types and functions > cell types and functions organs, tissues, organelles, cell types and functions organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > senescence
CSHL Authors:	Egeblad, Mikala Lowe, Scott W. Adrover, Jose M.
Communities:	CSHL labs > Egeblad lab CSHL labs > Lowe lab CSHL Cancer Center Program CSHL Cancer Center Program > Cellular Communication in Cancer Program CSHL Cancer Center Shared Resources > Animal Services CSHL Cancer Center Shared Resources > Animal Tissue and Imaging Service
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	27 October 2022
Date Deposited:	08 Nov 2022 16:23
Last Modified:	01 May 2024 19:12
PMCID:	PMC9901536
URI:	https://repository.cshl.edu/id/eprint/40748

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