Despite recent advances in the treatment of metastatic castration-resistant prostate cancer (mCRPC), agents that provide durable disease control and long-term survival are still needed. It is a fact that a tumor-induced immunosuppressive status (mediated by aberrant activation of inhibitory immune checkpoint pathways as a mechanism to evade host immune surveillance) plays a crucial role in the pathogenesis of cancer, including prostate cancer (PC), making CRPC patients suitable candidates for immunotherapy. Therefore, growing interest of anticancer research aims at blocking immune checkpoints (mainly targeting CTLA-4 and PD1/PD-L1 pathways) to restore and enhance cellular-mediated antitumor immunity and achieve durable tumor regression. In this review, we describe the current knowledge regarding the role of immune checkpoints in mediating PC progression, focusing on CTLA-4 and PD1 pathways. We also provide current clinical data available, an update on ongoing trials of immune checkpoint inhibitors in PC. Finally, we discuss the necessity to identify prognostic and predictive biomarkers of immune activity, and we analyze new immune checkpoints with a role as promising targets for PC therapy.
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Oncology reviews. 2016 Apr 15*** epublish ***
Alessandra Modena, Chiara Ciccarese, Roberto Iacovelli, Matteo Brunelli, Rodolfo Montironi, Michelangelo Fiorentino, Giampaolo Tortora, Francesco Massari
Medical Oncology, University-Hospital of Verona , Verona, Italy., Medical Oncology, University-Hospital of Verona , Verona, Italy., Medical Oncology, University-Hospital of Verona , Verona, Italy., Department of Pathology and Diagnostic, University-Hospital of Verona , Verona, Italy., Section of Pathological Anatomy, Polytechnic University of Marche Region, School of Medicine , Ancona, Italy., Pathology Service, Addarii Institute of Oncology, S. Orsola-Malpighi Hospital , Bologna, Italy., Medical Oncology, University-Hospital of Verona , Verona, Italy., Division of Oncology, S. Orsola-Malpighi Hospital , Bologna, Italy.