Combining Radiation-Treated Tumor Vaccines With Mn-MOF Nanoadjuvants to Amplify Radiation Induced Anti-Tumor Immune Responses.

Radiotherapy-induced mutations are critical for neoantigen generation and the initiation of in situ vaccine mediated immune responses; however, their efficacy is severely limited by the immunosuppressive tumor microenvironment. Here, genomic analysis demonstrated that B16F10 tumor cells subjected to in vitro irradiation faithfully recapitulate part of the radiotherapy-induced mutational landscape observed in subcutaneous tumor models. Based on these findings, a biomimetic cancer vaccine was developed through the integration of RT-treated tumor cell membranes and manganese-based metal organic framework nanoadjuvants (Mn@RM). Mn@RM can deliver RT-induced membrane proteins directly to lymph nodes in order to potentiate the in situ vaccine immune response. Moreover, Mn-MOF nanoadjuvants enhanced antigen presentation efficiency by nearly two-fold through activation of the cGAS-STING pathway in dendritic cells, while Mn@RM further optimized the lymph node immune microenvironment to promote robust anti-tumor immunity. When combined with radiotherapy and PD-1 immune checkpoint blockade, Mn@RM demonstrates excellent synergistic tumor treatment effect. Overall, this study offers a promising and clinically translatable platform to augment radiotherapy induced anti-tumor immunity, particularly for patients receiving radiotherapy in conjunction with surgical interventions.