BACKGROUND: We performed profiling of the immune microenvironment of castration-resistant (CRPC) and castration-sensitive (CSPC) prostate cancer (PC) in order to identify novel targets for immunotherapy. METHODS: PD-L1 and CD3/CD8 immunohistochemistry, PD-L1/2 fluorescent in situ hybridization, tumor mutation burden, microsatellite instability, and RNA-seq of 395 immune-related genes were performed in 19 CRPC and CSPC. Targeted genomic sequencing and fusion analysis were performed in 17 of these specimens. RESULTS: CD276, PVR, and NECTIN2 were highly expressed in PC. Comparison of CRPC versus CSPC and primary versus metastatic tissue revealed the differential expression of immunostimulatory, immunosuppressive, and epithelial-to-mesenchymal transition (EMT)-related genes. Unsupervised clustering of differentially expressed genes yielded two final clusters best segregated by CRPC and CSPC status. CONCLUSION: CD276 and the alternative checkpoint inhibition PVR/NECTIN2/CD226/TIGIT pathway emerged as relevant to PC checkpoint inhibition target development.
BACKGROUND: We performed profiling of the immune microenvironment of castration-resistant (CRPC) and castration-sensitive (CSPC) prostate cancer (PC) in order to identify novel targets for immunotherapy. METHODS:PD-L1 and CD3/CD8 immunohistochemistry, PD-L1/2 fluorescent in situ hybridization, tumor mutation burden, microsatellite instability, and RNA-seq of 395 immune-related genes were performed in 19 CRPC and CSPC. Targeted genomic sequencing and fusion analysis were performed in 17 of these specimens. RESULTS:CD276, PVR, and NECTIN2 were highly expressed in PC. Comparison of CRPC versus CSPC and primary versus metastatic tissue revealed the differential expression of immunostimulatory, immunosuppressive, and epithelial-to-mesenchymal transition (EMT)-related genes. Unsupervised clustering of differentially expressed genes yielded two final clusters best segregated by CRPC and CSPC status. CONCLUSION:CD276 and the alternative checkpoint inhibition PVR/NECTIN2/CD226/TIGIT pathway emerged as relevant to PC checkpoint inhibition target development.
Authors: Nathan J Mackenzie; Clarissa Nicholls; Abby R Templeton; Mahasha Pj Perera; Penny L Jeffery; Kate Zimmermann; Arutha Kulasinghe; Tony J Kenna; Ian Vela; Elizabeth D Williams; Patrick B Thomas Journal: Clin Transl Immunology Date: 2022-06-26
Authors: Jacklyn N Hellwege; Sarah Stallings; Eric S Torstenson; Robert Carroll; Kenneth M Borthwick; Murray H Brilliant; David Crosslin; Adam Gordon; George Hripcsak; Gail P Jarvik; James G Linneman; Parimala Devi; Peggy L Peissig; Patrick A M Sleiman; Hakon Hakonarson; Marylyn D Ritchie; Shefali Setia Verma; Ning Shang; Josh C Denny; Dan M Roden; Digna R Velez Edwards; Todd L Edwards Journal: Sci Rep Date: 2019-04-15 Impact factor: 4.379
Authors: Eddie Luidy Imada; Diego Fernando Sanchez; Wikum Dinalankara; Thiago Vidotto; Ericka M Ebot; Svitlana Tyekucheva; Gloria Regina Franco; Lorelei Ann Mucci; Massimo Loda; Edward Matthew Schaeffer; Tamara Lotan; Luigi Marchionni Journal: BMC Cancer Date: 2021-07-26 Impact factor: 4.430