Therapy-induced senescent cancer cells contribute to cancer progression by promoting ribophorin 1-dependent PD-L1 upregulation.

ABSTRACT: Conventional chemotherapy- and radiotherapy-induced cancer senescence, which is characterized by poor proliferation, drug resistance, and senescence-associated secretory phenotype, has gained attention as contributing to cancer relapse and the development of an immunosuppressive tumor microenvironment. However, the association between cancer senescence and anti-tumor immunity is not fully understood. Here, we demonstrate that senescent cancer cells increase the level of PD-L1 by promoting its transcription and glycosylation. We identify ribophorin 1 as a key regulator of PD-L1 glycosylation during cancer senescence. Ribophorin 1 depletion reduces this elevated level of PD-L1 through the ER-lysosome-associated degradation pathway, thereby increasing the susceptibility of senescent cancer ce

SUBMITTER: Hwang HJ 

PROVIDER: S-EPMC11699195 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature