Versatile Co-Engineering of Immunogenic Cell Death-Primed Dead Tumor Cell Bodies With Tumor-Activated MnO2 for cGAS-STING-Potentiated Personalized Immunotherapy.

Immunogenic cell death (ICD)-based whole-cell personalized cancer immunotherapies present full tumor antigens but suffer from poor immunogenicity, early clearance, and a glutathione (GSH)-rich immunosuppressive tumor microenvironment (TME). Here, we report a TME-responsive immunotherapeutic platform, DTBEI@CS@MnO2, which integrates immunogenicity-enhanced dead tumor cell bodies (DTBEI) with Mn2 +-potentiated innate immunity. Tumor cells preloaded with indocyanine green (ICG) are sequentially functionalized with a chitosan (CS) interlayer followed by MnO2 adsorption (CS@MnO2) via electrostatic interactions. Upon near-infrared laser irradiation, ICG-mediated photodynamic/photothermal effect induces potent ICD, generating DTBEI. Within the acidic and GSH-enriched TME, the CS@MnO2 coating disassembles to release DTBEI and MnO2. DTBEI provides endogenous antigens and ICD-associated danger signals, while MnO2 is reduced by GSH to Mn2 +. The resulting Mn2 + amplifies DTBEI- and tumor-derived deoxyribonucleic acid-triggered cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) activation and downstream immune-stimulatory effects, thereby synergistically promoting dendritic cell maturation, antigen cross-presentation, and tumor-specific T-cell priming. Consequently, DTBEI@CS@MnO2 elicits durable anti-tumor immunity, effectively inhibiting tumor growth and suppressing recurrence and metastasis, while establishing T-cell memory responses. Importantly, this strategy shows broad applicability in multiple tumor models, including CT26 colon cancer, 4T1 breast cancer, and B16F10 melanoma, while maintaining favorable biocompatibility. Overall, these findings highlight a materials-based approach for personalized cancer immunotherapy.