Mannose Receptor–positive Macrophage Infiltration Correlates with Prostate Cancer Onset and Metastatic Castration-resistant Disease

Background: M2 tumor-associated macrophages (M2-TAMs) can suppress inflammation in the tumor microenvironment and have been reported to modulate cancer progression. We and others have previously reported M2-TAM infiltration in metastatic castration-resistant prostate cancer (mCRPC). Objective: To determine whether the extent of M2-TAM infiltration correlates with PC aggressiveness. Design, setting, and participants: Normal prostate tissue, localized PC, and mCRPC samples from 192 patients were retrospectively analyzed. Outcome measurements and statistical analysis: We analytically validated an immunohistochemistry assay for detection of the human mannose receptor (CD206) to assess M2 macrophage involvement. Results and limitations: Multiplex immunofluorescent staining showed that a small fraction of CD206 staining co-localized with the endothelial cells of lymphatic vessels, while the vast majority of staining occurred in CD68-positive macrophages. The area fraction of staining for CD206-positive macrophages increased in a stepwise fashion from normal (ie, no inflammation) prostate tissue, to primary untreated carcinomas, to hormone-naïve regional lymph node metastases, to mCRPC. Complementary studies using flow cytometry confirmed CD206-positive M2-TAM infiltration. Limitations include the small number of rapid autopsy samples and the lack of neuroendocrine PC samples. Conclusions: Our results revealed a progressive increase in CD206-positive macrophages from normal prostate to mCRPC. Given the immunosuppressive nature of macrophages and the lack of clinical success of immunotherapy for PC patients, our results provide a rationale for therapeutic targeting of macrophages in the PC microenvironment as a potential method to augment immunotherapeutic responses. Patient summary: In this report we used 192 prostate cancer samples to determine if M2 macrophage infiltration is correlated with castration resistance in prostate cancer.