Many studies have investigated the potential prognostic and predictive role of PD-L1 in prostatic carcinoma (PC). We performed a systematic literature review (PRISMA guidelines) to critically evaluate human tissue-based studies (immunohistochemistry, molecular analysis, etc. ), experimental research (cell lines, mouse models), and clinical trials. Despite some controversial results and study limitations, PD-L1 expression by tumor cells may be related to clinic-pathologic features of adverse outcome, including advanced tumor stage (high pT, presence of lymph node, and distant metastases), positivity of surgical margins, high Grade Group, and castration resistance. Different PD-L1 positivity rates may be observed in matched primary PCs and various metastatic sites of the same patients. Over-fixation, type/duration of decalcification, and PD-L1 antibody clone may influence the immunohistochemical analysis of PD-L1 on bone metastases. PD-L1 seemed expressed more frequently by castration-resistant PCs (49%) as compared to hormone-sensitive PCs (17%). Some series found that PD-L1 positivity was associated with decreased time to castration resistance. Treatment with ipilimumab, cyclophosphamide/GVAX/degarelix, or degarelix alone may increase PD-L1 expression. Correlation of PD-L1 positivity with overall survival and outcomes related to tumor recurrence were rarely investigated; the few analyzed series produced conflicting results and sometimes showed limitations. Further studies are required. The testing and scoring of PD-L1 should be standardized.
Cells. 2021 Nov 14*** epublish ***
Andrea Palicelli, Martina Bonacini, Stefania Croci, Cristina Magi-Galluzzi, Sofia Cañete-Portillo, Alcides Chaux, Alessandra Bisagni, Eleonora Zanetti, Dario De Biase, Beatrice Melli, Francesca Sanguedolce, Magda Zanelli, Maria Paola Bonasoni, Loredana De Marco, Alessandra Soriano, Stefano Ascani, Maurizio Zizzo, Carolina Castro Ruiz, Antonio De Leo, Guido Giordano, Matteo Landriscina, Giuseppe Carrieri, Luigi Cormio, Daniel M Berney, Jatin Gandhi, Giacomo Santandrea, Maria Carolina Gelli, Alessandro Tafuni, Moira Ragazzi
Pathology Unit, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy., Clinical Immunology, Allergy and Advanced Biotechnologies Unit, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy., Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA., Department of Scientific Research, School of Postgraduate Studies, Norte University, Asunción 1614, Paraguay., Department of Pharmacy and Biotechnology (FABIT), University of Bologna, 40126 Bologna, Italy., Fertility Center, Department of Obstetrics and Gynecology, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy., Pathology Unit, Policlinico Riuniti, University of Foggia, 71122 Foggia, Italy., Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA., Pathology Unit, Azienda Ospedaliera Santa Maria di Terni, University of Perugia, 05100 Terni, Italy., Surgical Oncology Unit, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy., Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, 41121 Modena, Italy., Molecular Diagnostic Unit, Azienda USL Bologna, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, 40138 Bologna, Italy., Medical Oncology Unit, Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy., Department of Urology and Renal Transplantation, University of Foggia, 71122 Foggia, Italy., Barts Cancer Institute, Queen Mary University of London, London EC1M 5PZ, UK., Department of Pathology and Laboratory Medicine, University of Washington, Seattle, WA 98195, USA.