This study investigates the immunogenicity of doxorubicin-induced tumor cell death. The authors found that doxorubicin (DX) can induce immunogenic cell death in tumor cells, which can elicit an effective antitumor immune response without the need for adjuvants. Caspase activation is crucial for the immunogenicity of DX-induced cell death, as caspase inhibitors or transfection with the caspase inhibitor p35 reduced the immunogenicity of dying tumor cells. Depletion of dendritic cells (DCs) or CD8+ T cells abolished the immune response against DX-treated apoptotic tumor cells in vivo. Freshly excised tumors treated with DX became immunogenic in vitro and could trigger regression of established tumors in immunocompetent mice. These findings suggest a strategy for generating cancer vaccines and stimulating anti-neoplastic immune responses in vivo.This study investigates the immunogenicity of doxorubicin-induced tumor cell death. The authors found that doxorubicin (DX) can induce immunogenic cell death in tumor cells, which can elicit an effective antitumor immune response without the need for adjuvants. Caspase activation is crucial for the immunogenicity of DX-induced cell death, as caspase inhibitors or transfection with the caspase inhibitor p35 reduced the immunogenicity of dying tumor cells. Depletion of dendritic cells (DCs) or CD8+ T cells abolished the immune response against DX-treated apoptotic tumor cells in vivo. Freshly excised tumors treated with DX became immunogenic in vitro and could trigger regression of established tumors in immunocompetent mice. These findings suggest a strategy for generating cancer vaccines and stimulating anti-neoplastic immune responses in vivo.