Blocking macrophage phagocytosis of tumor cells by anti-CD47 antibody (Ab) has demonstrated therapeutic efficacy in xenograft models. We have observed that in an immunocompetent host, a CTL adaptive response is essential for immungenic tumor regression after anti-CD47 Ab treatment. Furthermore, anti-CD47 Ab treatment promotes DC but not macrophage-mediated cross priming of CTLs in a type I IFN dependent fashion. In addition, we found that anti-CD47 Ab-mediated immunity requires the functional adaptor protein STING, but not MyD88, suggesting that cytosolic sensing of DNA from tumor cells is enhanced by anti-CD47 Ab treatment futher bridging the innate and adaptive responses. Importantly, we observed that the timing of standard chemotherapeutics impacts anti-CD47 Ab-initiated anti-tumor immunity. Together, our study reveals that anti-CD47 antibody can trigger DNA sensing pathway for adaptive immune-mediated destruction of immungenic tumors.

Citation Format: Meng Xu. Unmasking cancer to innate sensing by anti-CD47 antibody triggers adaptive immune-mediated destruction of immunogenic tumors. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr A155.