Irradiated senescent tumor cells-inspired vaccine for boosting anti-tumor immunity

Cancer vaccines are often limited by insufficient antigen presentation, T cell dysfunction, and an immunosuppressive tumor microenvironment. While whole tumor cell vaccines encompass the full antigenic repertoire, their clinical application is constrained by low immunogenicity and potential oncogenic risks. Here, we present a senescent tumor cells (SenTCs) vaccine generated via irradiation. Mechanistically, SenTCs enhance MHC-I antigen presentation through suppression of KDM1A and enrichment of H3K4me2 at MHC-I promoter regions. SenTCs promote innate immune activation, remodel the tumor microenvironment, and increase T cell infiltration, leading to reduced tumor growth in murine models. Notably, combination with a KDM1A inhibitor further improves anti-tumor efficacy compared to monotherapy. Collectively, these findings provide mechanistic insight into senescence-associated immune modulation and highlight the potential of SenTCs-based strategies for cancer immunotherapy.