Abstract 4582: Mannose receptor positive macrophage infiltrate correlates with prostate cancer onset and metastatic castration-resistant disease

Abstract

M2-Tumor Associated macrophages (M2-TAMs) can suppress inflammation within the tumor microenvironment and have been reported to modulate cancer progression. We and others have previously reported infiltration of M2 macrophages in metastatic castrate-resistant prostate cancers (mCRPC). The objective of this study was to determine whether the extent of M2 macrophage infiltration correlates with prostate cancer aggressiveness, we applied immunohistochemistry to normal prostatic tissue, localized prostate cancer and metastatic castrate-resistant prostate cancer (mCRPC) from 192 patients. To assess M2 macrophage involvement, we analytically validated an IHC assay to detect the human mannose receptor (CD206). Also, we used multiplex immunofluorescent staining to show that a small fraction of CD206 staining co-localizes with endothelial cells of lymphatic vessels, while the vast majority of staining occurs in CD68-positive macrophages. The area fraction of staining for CD206-positive macrophages increased in a stepwise fashion going from normal (i.e. non-inflammation) prostatic tissue, to primary untreated carcinomas, to hormone naive regional lymph node metastases to castration resistant prostate cancer. Complimentary studies using flow cytometry confirmed CD206-positive M2-TAM infiltration. Altogether, this study revealed a progressive increase in CD206-positive macrophages from normal prostate to metastatic CRPC. Given the immunosuppressive nature of these cells and lack of clinical success of immunotherapy for prostate cancer patients, our results provide a rationale for therapeutic development to deplete these cells in the prostate cancer microenvironment as a potential method to augment immunotherapeutic approaches in prostate cancer. Citation Format: Jelani C. Zarif, Javier A. Baena-Del Valle, Jessica L. Hicks, Christopher M. Heaphy, Igor Vidal, Jacob Luo, Tamara L. Lotan, Jody E. Hooper, William B. Isaacs, Kenneth J. Pienta, Angelo M. De Marzo. Mannose receptor positive macrophage infiltrate correlates with prostate cancer onset and metastatic castration-resistant disease [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4582.