LAUSR

Introduction: Peritoneal immune system plays an important role during the peritoneal dissemination of colon cancers. Therefore, tumor-induced T cell anergy in peritoneal cavity could lead to immune evasion and the progression of peritoneal carcinomatosis. Here, we aimed to reverse the immune evasion in peritoneal cavity and effectively suppress the peritoneal carcinomatosis of colon cancer by STING-based immunotherapy. Methods: We established an animal model of peritoneal carcinomatosis by intraperitoneal injection of MC38 colon cancer cells to C57BL/6 mice. Temporal changes in peritoneal immune microenvironment during peritoneal tumor dissemination were first characterized by analyzing tumor nodules, malignant ascites, and peritoneum lavage by flow cytometry. Then, tumor-bearing mice were treated with either STING agonist (ADU-S100), and/or anti-PD-1 antibody. Tumor burden and the volume of ascites were assessed after the treatment. The tumors were analyzed with flow cytometric, histologic, and RNA sequencing analyses. Results: The intraperitoneal inoculation of MC38 colon cancer cells led to dramatic immune cell changes in peritoneal cavity. While the number of myeloid-derived suppressor cells (MDSCs) were markedly increased, the number of CD8+ T cells and dendritic cells gradually decreased after initial influx in the peritoneal cavity. Treatment with STING agonist remarkably suppressed the growth of peritoneal seeding nodules (75%). Moreover, normalization and reduction of peritoneal tumor blood vessels resulted in an overt decrease in malignant ascites (85%) in the peritoneal cavity after STING agonist treatment. In addition, the number of dendritic cells and CD8+ T cells had markedly increased, but that of MDSCs was decreased in the peritoneal cavity. Moreover, the number of IFN-gamma-secreting cytotoxic T cells were increased in tumor nodules and peritoneal cavity after STING agonist treatment. Finally, the combination immunotherapy of STING agonist and anti-PD1 antibody induced stronger adaptive immunity against peritoneal carcinomatosis than monotherapy and showed potent anti-cancer activity with reduced ascites formation. Conclusion: STING immunotherapy can normalize peritoneal tumor vasculature and immune system, and synergize with immune checkpoint blockade to control peritoneal carcinomatosis of colon cancer. Citation Format: Hannah Yang, Seung Jun Lee, Yu Seong Lee, Won Suk Lee, So Jung Kong, Beodeul Kang, Hong Jae Chon, Chan Kim. Peritoneal immune evasion can be overcome with STING agonist treatment in peritoneal carcinomatosis of colon cancer [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 2838.