CGAS-STING pathway mediates antitumor immunity of tumor cryoablation in syngeneic murine Rhabdomyosarcoma

Abstract

Abstract Tumor cryoablation, a medical procedure that utilizes ultra-cold temperatures to destroy in situ local tumor tissues, has been established for cure of many tumor types and for stimulation of the immune system. The mechanism of immune response to tumor cryoabltion are not well defined. To understand the molecular pathway of immune activation by cryoablation, we performed comprehensive analyses on the impact of tumor cryoablation on mononuclear phagocytic lineage cells and the antitumor immunity. Here, we show that cryoablation of a murine Rhabdomyosarcoma (RMS) tumor, an aggressive sarcoma affecting children and young adults, was able to induce the regression of tumor and the upregulation of the critical immune cytokines/chemokines profile and maturation markers of CD11c+ DCs. Moreover, cryoablation of RMS tumor initiates cGAS-STING signaling activation and type I interferon production in CD11c+ DCs, which are consequential in pro-inflammatory tumor microenvironment (TME). We also report that antitumor effects of cryoablation were more inhibitive, but not completely abrogated, in STING-deficient mice comparing with wild-type mice, indicating that both host-derived and tumor-intrinsic cGAS-STING signaling plays an important role in antitumor effects of tumor cryoablation. Taken together, our results demonstrate that tumor cryoablation induces antitumor immunity via cGAS-STING signaling in syngeneic Rhabdomyosarcoma (RMS) tumor, and this approach may help guide future immunotherapy to improve cancer treatment outcomes.