The James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Oncology, Johns Hopkins School of Medicine and The Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA.
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Pathology and Laboratory Medicine, Fundacion Santa Fe de Bogota University Hospital, Bogota, Colombia.
Eur Urol Oncol. 2019 Jul;2(4):429-436. doi: 10.1016/j.euo.2018.09.014. Epub 2018 Oct 19.
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).
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.
We analytically validated an immunohistochemistry assay for detection of the human mannose receptor (CD206) to assess M2 macrophage involvement.
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.
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.
In this report we used 192 prostate cancer samples to determine if M2 macrophage infiltration is correlated with castration resistance in prostate cancer.
M2 肿瘤相关巨噬细胞（M2-TAMs）可以抑制肿瘤微环境中的炎症，并已被报道调节癌症进展。我们和其他人之前曾报道过转移性去势抵抗性前列腺癌（mCRPC）中的 M2-TAM 浸润。
确定 M2-TAM 浸润的程度是否与前列腺癌的侵袭性相关。
设计、设置和参与者：回顾性分析了 192 名患者的正常前列腺组织、局限性前列腺癌和 mCRPC 样本。
我们对一种用于检测人甘露糖受体（CD206）的免疫组织化学检测进行了分析验证，以评估 M2 巨噬细胞的参与。
多重免疫荧光染色显示，一小部分 CD206 染色与淋巴管的内皮细胞共定位，而绝大多数染色发生在 CD68 阳性的巨噬细胞中。CD206 阳性巨噬细胞的染色面积分数从正常（即无炎症）前列腺组织、原发性未治疗的癌、激素-naive 区域淋巴结转移到 mCRPC 呈逐步增加的趋势。使用流式细胞术进行的补充研究证实了 CD206 阳性 M2-TAM 的浸润。局限性包括快速尸检样本数量较少以及缺乏神经内分泌前列腺癌样本。
我们的结果显示，从正常前列腺到 mCRPC，CD206 阳性巨噬细胞逐渐增加。鉴于巨噬细胞的免疫抑制性质以及免疫疗法治疗前列腺癌患者的临床效果不佳，我们的结果为在前列腺癌微环境中靶向巨噬细胞作为增强免疫治疗反应的潜在方法提供了依据。
在本报告中，我们使用了 192 个前列腺癌样本来确定 M2 巨噬细胞浸润是否与前列腺癌的去势抵抗相关。
