Yang Shijie, Zhang Qiuyang, Liu Sen, Wang Alun R, You Zongbing
Department of Structural and Cellular Biology, Tulane UniversityNew Orleans, LA, USA; Department of Urology, The Third Hospital of Hebei Medical UniversityShijiazhuang, China.
Department of Structural and Cellular Biology, Tulane University New Orleans, LA, USA.
Am J Clin Exp Urol. 2016 Jan 28;4(1):1-8. eCollection 2016.
Programmed cell death protein 1 (PD-1) and its ligands PD-L1 and PD-L2 play critical roles in maintaining an immunosuppressive tumor microenvironment. The purpose of the present study was to assess expression of PD-1, PD-L1, and PD-L2 in mouse prostate tumors. A total of 33 mouse prostate tumors derived from Pten-null mice were examined using immunohistochemical staining for PD-1, PD-L1, and PD-L2. The animals were either with interleukin-17 receptor c (Il-17rc) wild-type or knockout genotype, or fed with regular diet or high-fat diet to 30 weeks of age. We found that Il-17rc wild-type mouse prostate tumors had significantly higher levels of PD-1, PD-L1, and PD-L2 than Il-17rc knockout mouse prostate tumors. High-fat diet-induced obese mice had significantly higher levels of PD-1, PD-L1, and PD-L2 in their prostate tumors than lean mice fed with regular diet. Increased expression of PD-1, PD-L1, and PD-L2 was associated with increased number of invasive prostate tumors formed in the Il-17rc wild-type and obese mice compared to the Il-17rc knockout and lean mice, respectively. Our findings suggest that expression of PD-1, PD-L1, and PD-L2 may enhance development of mouse prostate cancer through creating an immunosuppressive tumor microenvironment.
程序性细胞死亡蛋白1(PD-1)及其配体PD-L1和PD-L2在维持免疫抑制性肿瘤微环境中发挥着关键作用。本研究的目的是评估PD-1、PD-L1和PD-L2在小鼠前列腺肿瘤中的表达情况。使用针对PD-1、PD-L1和PD-L2的免疫组织化学染色检查了总共33个源自Pten基因缺失小鼠的小鼠前列腺肿瘤。这些动物要么具有白细胞介素-17受体c(Il-17rc)野生型或敲除基因型,要么喂食常规饮食或高脂饮食至30周龄。我们发现,Il-17rc野生型小鼠前列腺肿瘤中PD-1、PD-L1和PD-L2的水平显著高于Il-17rc敲除小鼠前列腺肿瘤。高脂饮食诱导的肥胖小鼠前列腺肿瘤中PD-1、PD-L1和PD-L2的水平显著高于喂食常规饮食的瘦小鼠。与Il-17rc敲除小鼠和瘦小鼠相比,Il-17rc野生型小鼠和肥胖小鼠中PD-1、PD-L1和PD-L2表达的增加分别与侵袭性前列腺肿瘤形成数量的增加有关。我们的研究结果表明,PD-1、PD-L1和PD-L2的表达可能通过创造免疫抑制性肿瘤微环境来促进小鼠前列腺癌的发展。