Identification of targets for prostate cancer immunotherapy

• Published in: The Prostate 2019-04, Vol.79 (5), p.498-505
• Main Authors: Papanicolau‐Sengos, Antonios, Yang, Yuanquan, Pabla, Sarabjot, Lenzo, Felicia L., Kato, Shumei, Kurzrock, Razelle, DePietro, Paul, Nesline, Mary, Conroy, Jeffrey, Glenn, Sean, Chatta, Gurkamal, Morrison, Carl
• Format: Article
• Language: English
• Subjects: Aged; aggressive prostate cancer; Antigens, CD - biosynthesis; Antigens, CD - genetics; Antigens, CD - immunology; B7-H1 Antigen - biosynthesis; B7-H1 Antigen - genetics; B7-H1 Antigen - immunology; Cancer immunotherapy; Castration; castration‐resistant prostate cancer; castration‐sensitive prostate cancer; CD226; CD276; CD3 antigen; CD8 antigen; Fluorescence in situ hybridization; Humans; Immunohistochemistry; Immunostimulation; Immunotherapy; Immunotherapy - methods; Male; Mesenchyme; Metastases; Microsatellite Instability; Middle Aged; NECTIN2; Nectins - biosynthesis; Nectins - genetics; Nectins - immunology; PD-L1 protein; Programmed Cell Death 1 Ligand 2 Protein - biosynthesis; Programmed Cell Death 1 Ligand 2 Protein - genetics; Programmed Cell Death 1 Ligand 2 Protein - immunology; Prostate cancer; Prostatic Neoplasms - genetics; Prostatic Neoplasms - immunology; Prostatic Neoplasms - therapy; Prostatic Neoplasms, Castration-Resistant - genetics; Prostatic Neoplasms, Castration-Resistant - immunology; Prostatic Neoplasms, Castration-Resistant - therapy; PVR; Ribonucleic acid; RNA; RNA, Neoplasm - biosynthesis; RNA, Neoplasm - genetics; RNA, Neoplasm - immunology; TIGIT; TOR Serine-Threonine Kinases - biosynthesis; TOR Serine-Threonine Kinases - genetics; TOR Serine-Threonine Kinases - immunology; Tumor Microenvironment - immunology
• ISSN: 0270-4137; 1097-0045
• DOI: 10.1002/pros.23756

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.