Abstract 3810: Ovarian tumor-induced changes in macrophage phenotype are associated with tumor metastasis

Abstract

Abstract Background: Ovarian cancer (OVCA) differs from other gynecologic malignancies in its dissemination pattern where the tumor migrates in a diffuse intrapelvic and -abdominal manner. OVCA also triggers a variety of cellular and/or humoral immune responses to a variety of tumor-associated proteins. OVCA is mostly diagnosed at late stages where tumor has already metastasized, indicating an escape from immune responses. Despite several immune response factors, ovarian tumor metastasizing to omentum indicates presence of one or more immune evasion mechanisms. Immune system recognizes and eliminates pathogenic products and tumor cells and macrophages play a critical role in this process. Macrophages in tumor condition express anti-inflammatory cytokines that induce immune suppression. Cellular immune response maximizes killing efficacy of macrophages and proliferation of CD8+ T cells. M2 macrophages are tumor-associated macrophages involved in active growth and progression of tumors. However, the mechanism of ovarian tumor-induced changes in M1 macrophages to M2 phenotype is not well understood. Therefore, the goal of our study was to determine the tumor-induced changes in macrophage phenotype and cytotoxic T cells in association with OVCA metastasis. Materials and Methods: This study was performed in exploratory design using ovarian specimen from normal subjects (60-80 years, n=10) and ovarian malignant tumors at early (n=16, 4 from each histologic type of OVCA) and late stages (n =20) as well as omental tissues from normal (n=3) and OVCA patients (n= 3). Tissue specimen were processed for immunohistochemistry (IHC), Western blotting (WB) and gene expression studies. Expression of M1 and M2 macrophages, CD8 and PI3K was examined by immunohistochemistry (IHC), Western blotting (WB) and qPCR. Results: Compared with normal ovaries, more M1 and M2 macrophages were localized in tumor tissues. However, compared with early-stage OVCA, the frequency of M2 macrophages was significantly higher in ovarian tumors and omental tissues at late OVCA. Intensity of PI3K was also higher in ovarian tumors and omental tissues at late OVCA compared with normal ovarian tissues. Frequency of CD8+T cells was higher in tumor ovarian samples in comparison with normal ovarian tissues. Conclusion: Results of this study suggest that the growth and metastasis of ovarian tumors are associated with increased conversion of M1 macrophages to M2 phenotype. This change in macrophage phenotype may be mediated by the increase in PI3K expression. Support: Swim Across America. Citation Format: Aparna Yellapa, Pincas Bitterman, Sameer Sharma, Sanjib Basu, Animesh Barua. Ovarian tumor-induced changes in macrophage phenotype are associated with tumor metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3810.