Abstract
Abstract Over the past 10-15 years, focus on the immune system has reinvigorated cancer research and oncology. Both clinical and experimental evidence generated during this time has shown that immune cells and their molecular mediators represent viable targets for therapeutic manipulation. The immune cell composition of high-grade serous carcinoma (HGSC) consists primarily of macrophages and various T cell subsets. However, the functional contribution of each of these cell types is largely unknown. In order to gain insight into whether these cells are pro- or anti-tumorigenic, we generated tissue microarrays containing tumors from 169 patients with pretreated ovarian cancer and quantified the number of CD68+ macrophages in each biopsy. Tumors were divided into high- or low-infiltrated groups based on the median number of macrophages amongst all HGSCs. Interestingly, patients whose tumors were highly infiltrated with macrophages exhibited worsened overall survival, suggesting that macrophages function as pro-tumorigenic cells in these tumors. To investigate the role of macrophages in HGSC progression, we have begun to characterize their abundance and phenotype in tumors of Dicerflox/flox;Ptenflox/flox;Amhr2cre/+ mice, a genetically engineered mouse model of HGSC. Macrophages constituted the predominant stromal and immune cell population in both primary tumors and secondary metastatic lesions. By contrast, macrophages were only found at low frequency in normal oviduct and ovaries. Gene expression analysis of these Dicer/Pten-deficient mouse tumors also revealed the increase in many macrophage-associated genes, as compared with normal oviduct tissue. Taken together, our data from mice and humans strongly indicate a crucial role for macrophages in facilitating ovarian cancer progression. Current efforts are underway to understand how macrophages promote ovarian tumor progression. Citation Format: Tanja Pejovic, Yukie Bean, Jaeyeon Kim, Martin M. Matzuk, Seth B. Coffelt. Macrophage infiltration in high-grade serous carcinomas of humans and mice [abstract]. In: Proceedings of the 10th Biennial Ovarian Cancer Research Symposium; Sep 8-9, 2014; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(16 Suppl):Abstract nr POSTER-BIOL-1308.
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