Bacterialized tumor cells as vaccine.

Tumor vaccines represent a promising modality in cancer immunotherapy, but the limited immunogenicity of whole-tumor cell vaccines (WTCVs) restricts their clinical translation. Here, we developed a novel bacterialized tumor cell (BTC) vaccine by coating amino-functionalized bacterial lysates onto the surface of tumor cells, a process we define as "bacterialization". In vitro and in vivo experiments demonstrated that BTCs efficiently promote dendritic cell (DC) phagocytosis, maturation, and antigen cross-presentation, enhance DC migration to draining lymph nodes (DLNs), and remodel the DLN microenvironment by expanding tumor-specific CD8⁺ T cells and memory CD8⁺ T cells, while reducing terminally exhausted CD8⁺ T cells. BTC vaccination elicited robust tumor-specific cellular and humoral immunity, which synergistically suppressed tumor growth and metastasis in five syngeneic murine tumor models with negligible adverse effects. Furthermore, BTC vaccination reversed the immunosuppressive tumor microenvironment by increasing functional CD8⁺ T cell infiltration and reducing inhibitory immune subsets, and exhibited significant synergistic anti-tumor effects when combined with anti-PD-1 immune therapy. These findings demonstrate that BTCs represent a safe and effective novel WTCV candidate with strong clinical translation potential.