P-131 - Cancer immunotherapy with STING agonist and PD-1 immune checkpoint inhibitor effectively suppresses peritoneal carcinomatosis of colon cancer

Abstract

Introduction: Peritoneal carcinomatosis is a common but lethal clinical presentation of colorectal cancer, which is usually refractory to conventional chemotherapy. Stimulator of interferon genes (STING) signaling is an emerging therapeutic target in cancer immunotherapy because it strongly activates dendritic cells and leads to the activation of the adaptive immune response involving T cells in various cancers. Here, we aimed to explore the therapeutic potential of STING agonist therapy in peritoneal carcinomatosis of colon cancer. Methods: C57Bl6/ mice were intraperitoneally implanted with MC38 colon cancer cells to develop peritoneal carcinomatosis with malignant ascites. Tumor-bearing mice were treated with either STING agonist, ADU-S100, or anti-PD-1 antibody every three days. Tumor size, the volume of ascites, and peritoneum seedings were assessed after the treatment course. The tumor microenvironment was comprehensively analyzed with multiplex immunofluorescence imaging, flow cytometry, and RNA sequencing. Results: Treatment with STING agonist remarkably suppressed the growth of peritoneal seeding nodules. Moreover, normalization and reduction of peritoneal tumor blood vessels resulted in an overt decrease in malignant ascites in the peritoneal cavity after STING treatment. In the tumor microenvironment, the number of intratumoral CD8 + T cells had markedly increased and adaptive anti-tumor immunity was enhanced with STING treatment. Moreover, IFN-gamma-secreting cytotoxic T cells against MC38 tumor cells were increased with STING treatment. Finally, the combination treatment of STING agonist and anti-PD1 antibody elicited greater anti-tumor immunity than monotherapy and showed potent and durable anti-cancer efficacy. Conclusion: In conclusion, STING agonist therapy normalized peritoneal tumor blood vessels, enhanced anti-cancer immune response, and synergized with PD-1 immune checkpoint inhibitor therapy in peritoneal carcinomatosis of colon cancer.