Abstract 2527: Ovarian cancer ascites display altered immune environment featured by enhanced soluble factors and suppressive cellular context

Abstract

Abstract Background: Tumor microenvironment (TME) of epithelial ovarian cancer is unique among solid tumors as tumor cells create their "malignant ascites" TME. These ascites, acting as a complex mixture of soluble factors and cell components, are known to be rich in macrophages which were suggested to skew to a M2-like phenotype involved in resistance and metastases. However, while macrophages can adopt different phenotypes, it's now postulated that tumor-associated macrophages (TAM) from ovarian cancer patient ascites may even acquire mixed M1/M2 properties, providing a particular pro-inflammatory and tumor-promoting microenvironment. Characterization of cell composition along with the growth factors present in the microenvironment is thus crucial to understand ovarian cancer biology and more particularly the immunosuppressive pathways that would underlie the altered immune cell activity. Methods & Results: Through flow cytometry-based marker expression analysis and quantitation of soluble mediators in ovarian cancer ascites, we investigated here the cell component nature as well as the presence of several growth factors. While these ascites were interestingly enriched in major "immunosuppressive" cell subsets including T and myeloid populations, TAM were intriguingly shown to display a mixed phenotype characterized by high expression of CD163, unrelated to M1/M2 categorization since also expressing Arg1, CD80, and iNOS markers. The immunosuppressive phenotype was also linked to IL6, LIF and IL10 among other factors present in the ascitic environment. In order to assess their role in the occurrence of such an immunosuppressive cell status, soluble mediators were then investigated on healthy monocytes undergoing M1 polarization. We demonstrated that, while LIF did not directly affect IL6 and IL10 levels released by the cells, interestingly IL6 alone or in co-presence with LIF decreased IL6 supernatant content, with respect to the control. These changes were concomitant with a decrease and increase in the expression of CD80 and CD163, respectively. Furthermore, CD14 and CD206 were found to increase in the presence of IL6+/-LIF. Conclusion: All these data highlight a switching activity of IL6 skewing cells from M1 polarization and resulting in a proper macrophage phenotype exhibiting a mixed M1/M2 status and would suggest these ascite-containing factors as keys conferring an immunosuppressive cell phenotype. Altogether, these translational findings highlight ovarian patient-derived ascites as a valuable tool to understand the mechanisms of suppression and to allow for the identification of novel markers to develop innovative targeted therapies. Citation Format: Imane Nafia, Assia Chaibi, Christophe Rey, Jean-Philippe Guegan, Alban Bessede, Coriolan Lebreton, Antoine Italiano. Ovarian cancer ascites display altered immune environment featured by enhanced soluble factors and suppressive cellular context [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2527.