The powerful biology of senescence in cancer and aging



開催日時 2023年7月24日(月)14:00~15:00
開催場所 1号館講堂
講師 Scott W. Lowe
所属・職名 Chair, Cancer Biology and Genetics Program Sloan Kettering Institute
演題 The powerful biology of senescence in cancer and aging
世話人 主たる世話人 中西 真(癌防御シグナル分野)
       岩間 厚志(幹細胞分子医学分野)


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 (IFNγ). Compared with proliferating cells, senescent cells upregulate the IFNγ receptor, become hypersensitized to microenvironmental IFNγ, and more robustly induce the antigen-presenting machinery—effects also recapitulated in human tumor cells undergoing therapy-induced senescence. Disruption of IFNγ 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.