Senescent cells display an altered immunopeptidome and promote CD8-dependent antitumor immunity

Cellular senescence is a stress response known to activate innate immunity. However, how senescent cells interact with the adaptive immune system remains largely unexplored. Here, we show that senescent cells display an enhanced MHC class I antigen processing and presentation. Furthermore, senescent cells present an altered immunopeptidome including unique non-mutated antigens that can be recognized by specific CD8 T cells. Immunization of mice with senescent cancer cells triggers strong protective CD8-dependent antitumor responses, superior to immunogenic cell death. Similarly, induction of senescence in human primary cancer cells hyperactivates their cognate reactive CD8 T cell. Our study indicates that immunization with senescent cells provides a sustained source of antigens that strongly activate anti-tumor CD8 T cells.