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.
American journal of clinical and experimental urology. 2016 Jan 28*** epublish ***
Shijie Yang, Qiuyang Zhang, Sen Liu, Alun R Wang, Zongbing You
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., Department of Structural and Cellular Biology, Tulane University New Orleans, LA, USA., Department of Pathology and Laboratory Medicine, Tulane University New Orleans, LA, USA., Department of Structural and Cellular Biology, Tulane UniversityNew Orleans, LA, USA; Tulane Cancer Center and Louisiana Cancer Research Consortium, Tulane UniversityNew Orleans, LA, USA; Department of Orthopaedic Surgery, Tulane UniversityNew Orleans, LA, USA; Tulane Center for Stem Cell Research and Regenerative Medicine, Tulane UniversityNew Orleans, LA, USA; Tulane Center for Aging, Tulane UniversityNew Orleans, LA, USA.