The modulation of adaptive immune response by oncogene K-ras; mouse model of ovarian cancer

Purpose: Little is known about how oncogenes affect the immune response in tumor microenvironment (TME). In this study, we focused on how oncogenes modulate adaptive immune response of ovarian cancer with peritoneal carcinomatosis and investigated the difference between reproductive immunity and tumor immunity. Methods: K-ras was stably introduced intomurine ovarian cancer cell line: ID8. Each cell line was intra-peritoneal injected into mice, and the production of ascites was observed. The population of T cell and dendritic cell (DC) subsets of spleen and ascites was assessedbyCD8/CD4orCD11c/mPDCAdouble-stainedflowcytometry. Results: K-ras enhanced the production of ascites. Compared to control mice, the CD8/CD4 ratio was increased in the cancer induced ascites without any difference between ID8 and ID8Kras. CD11c high mPDCA negative DC subset was increased in the ID8-induced ascites, which was markedly decreased in the ID8Kras-induced ascites. There was no significant difference in the subset of T cell or DC of spleen. Conclusion: K-ras accelerated cancer progression by modulating immune response in TME. In the tumor immune system, oncogenes, being closely related to the modulation of TME, are responsible for its specific characteristics compared to the reproductive immunity.