Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland, USA.
Prostate. 2022 Dec;82(16):1505-1519. doi: 10.1002/pros.24424. Epub 2022 Aug 16.
Black men are two to three times more likely to die from prostate cancer (PCa) than White men. This disparity is due in part to discrepancies in socioeconomic status and access to quality care. Studies also suggest that differences in the prevalence of innate immune cells and heightened function in the tumor microenvironment of Black men may promote PCa aggressiveness.
We evaluated the spatial localization of and quantified CD66ce neutrophils by immunohistochemistry and CD68 (pan), CD80 (M1), and CD163 (M2) macrophages by RNA in situ hybridization on formalin-fixed paraffin-embedded tissues from organ donor "normal" prostate (n = 9) and radical prostatectomy (n = 38) tissues from Black and White men. Neutrophils were quantified in PCa and matched benign tissues in tissue microarray (TMA) sets comprised of 560 White and 371 Black men. Likewise, macrophages were quantified in TMA sets comprised of tissues from 60 White and 120 Black men. The phosphatase and tensin homolog (PTEN) and ETS transcription factor ERG (ERG) expression status of each TMA PCa case was assessed via immunohistochemistry. Finally, neutrophils and macrophage subsets were assessed in a TMA set comprised of distant metastatic PCa tissues collected at autopsy (n = 6) sampled across multiple sites.
CD66ce neutrophils were minimal in normal prostates, but were increased in PCa compared to benign tissues, in low grade compared to higher grade PCa, in PCa tissues from White compared to Black men, and in PCa with PTEN loss or ERG positivity. CD163 macrophages were the predominant macrophage subset in normal organ donor prostate tissues from both Black and White men and were significantly more abundant in organ donor compared to prostatectomy PCa tissues. CD68, CD80, and CD163 macrophages were significantly increased in cancer compared to benign tissues and in cancers with ERG positivity. CD68 and CD163 macrophages were increased in higher grade cancers compared to low grade cancer and CD80 expression was significantly higher in benign prostatectomy tissues from Black compared to White men.
Innate immune cell infiltration is increased in the prostate tumor microenvironment of both Black and White men, however the composition of innate immune cell infiltration may vary between races.
黑人男性死于前列腺癌（PCa）的可能性是白人男性的两到三倍。这种差异部分归因于社会经济地位的差异和获得高质量医疗保健的机会。研究还表明，黑人男性肿瘤微环境中固有免疫细胞的存在和功能增强的差异可能促进了 PCa 的侵袭性。
我们通过免疫组织化学评估了福尔马林固定石蜡包埋组织中 CD66ce 中性粒细胞的空间定位和定量，并通过 RNA 原位杂交评估了 CD68（pan）、CD80（M1）和 CD163（M2）巨噬细胞。从器官捐献者“正常”前列腺（n=9）和黑人男性和白人男性根治性前列腺切除术（n=38）组织中评估了 CD66ce 中性粒细胞和 CD80（M1）、CD163（M2）巨噬细胞的空间定位和定量。在由 560 名白人男性和 371 名黑人男性组成的组织微阵列（TMA）中，对 PCa 和匹配的良性组织中的中性粒细胞进行了定量分析。同样，在由 60 名白人男性和 120 名黑人男性组成的 TMA 组织中对巨噬细胞进行了定量分析。通过免疫组织化学评估了每个 TMA PCa 病例的磷酸酶和张力蛋白同源物（PTEN）和 ETS 转录因子 ERG（ERG）的表达状态。最后，在一组由尸检采集的远处转移性 PCa 组织组成的 TMA 中评估了中性粒细胞和巨噬细胞亚群（n=6），这些组织分布在多个部位。
CD66ce 中性粒细胞在正常前列腺中很少，但在 PCa 中与良性组织相比增加，在低级别 PCa 中与高级别 PCa 相比增加，在白人男性的 PCa 中与黑人男性的 PCa 相比增加，在具有 PTEN 缺失或 ERG 阳性的 PCa 中增加。CD163 巨噬细胞是黑人男性和白人男性正常供体前列腺组织中的主要巨噬细胞亚群，在供体组织中明显多于前列腺切除术 PCa 组织。与良性组织相比，CD68、CD80 和 CD163 巨噬细胞在癌症中明显增加，而在具有 ERG 阳性的癌症中则明显增加。与低级别癌症相比，CD68 和 CD163 巨噬细胞在高级别癌症中增加，而 CD80 表达在黑人男性的良性前列腺切除术组织中明显高于白人男性。
黑人男性和白人男性的前列腺肿瘤微环境中固有免疫细胞浸润增加，但是固有免疫细胞浸润的组成可能因种族而异。
