title: Immune Checkpoint Inhibitors and Prostate Cancer: A New Frontier?
abstract: 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.
authors.affiliation: Medical Oncology, University-Hospital of Verona , Verona, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Modena
authors.affiliation: Medical Oncology, University-Hospital of Verona , Verona, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Ciccarese
authors.affiliation: Medical Oncology, University-Hospital of Verona , Verona, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Iacovelli
authors.affiliation: Department of Pathology and Diagnostic, University-Hospital of Verona , Verona, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Brunelli
authors.affiliation: Section of Pathological Anatomy, Polytechnic University of Marche Region, School of Medicine , Ancona, Italy.
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Montironi
authors.affiliation: Pathology Service, Addarii Institute of Oncology, S. Orsola-Malpighi Hospital , Bologna, Italy.
authors.forename: Michelangelo
authors.initials: M
authors.lastname: Fiorentino
authors.affiliation: Medical Oncology, University-Hospital of Verona , Verona, Italy.
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Tortora
authors.affiliation: Division of Oncology, S. Orsola-Malpighi Hospital , Bologna, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Massari
keywords: CTLA-4; PD-1; PD-L1; Prostate cancer; immune checkpoint inhibitors; immunotherapy