Abstract 971: Effects of tumor cryo-ablation on cGAS-STING pathway and antitumor immunity in syngeneic murine rhabdomyosarcoma

Abstract

Abstract Even with current improvement in cancer therapy, tumor immunosuppressive microenvironment and metastatic tumors are important factors which have shown to be a challenge for cancer treatment. Thus, targeting the tumor microenvironment (TME) locally are required to modify the activation of innate immunity, which can provoke subsequent global adaptive anti-tumor immunity. Tumor cryo-ablation, a medical procedure that utilizes ultra-cold temperatures to destroy in situ local tumor tissues, has the capability to induce the release of immune danger signals that activate antigen-presenting cells to initiate the anti-tumor immunity. To understand the mechanism of immune activation by cryo-ablation, we performed comprehensive analyses on the effects of tumor cryo-ablation on mononuclear phagocytic lineage cells and the antitumor immunity. Here, we show that cryo-ablation of syngeneic Rhabdomyosarcoma (RMS) tumor, an aggressive sarcoma affecting children and young adults, was able to induce both the regression of tumor and the upregulation of the critical immune cytokines and chemokines profile. Moreover, cryo-ablation of RMS tumor initiates cGAS-STING signaling activation and type I interferon production in dendritic cells, which are consequential in pro-inflammatory TME. We also report that antitumor effects of cryo-ablation was more inhibitive, but not completely abrogated, in STING-deficient mice comparing with wild-type mice, demonstrating that both host-derived and tumor-intrinsic cGAS-STING signaling plays an important role in antitumor effects of tumor cryo-ablation. Ongoing experiments will address the efficacy of RMS tumor cryo-ablation on systemic anti-tumor immune activation leading to an abscopal effect on tumor regression at metastatic tumor. Taken together, our results demonstrate that tumor cryo-ablation affects antitumor immunity and cGAS-STING signaling in RMS tumor, and this approach may help guide future immunotherapy to improve cancer treatment outcomes. Citation Format: Mohammad Abdulaziz Alshebremi, Jay T. Myers, Daniel T. Kingsley, Alex Y. Huang. Effects of tumor cryo-ablation on cGAS-STING pathway and antitumor immunity in syngeneic murine rhabdomyosarcoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 971.