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

Abstract

BackgroundM2 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). ObjectiveTo determine whether the extent of M2-TAM infiltration correlates with PC aggressiveness. Design, setting, and participantsNormal prostate tissue, localized PC, and mCRPC samples from 192 patients were retrospectively analyzed. Outcome measurements and statistical analysisWe analytically validated an immunohistochemistry assay for detection of the human mannose receptor (CD206) to assess M2 macrophage involvement. Results and limitationsMultiplex 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. ConclusionsOur 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 summaryIn this report we used 192 prostate cancer samples to determine if M2 macrophage infiltration is correlated with castration resistance in prostate cancer.