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Immune checkpoint inhibitors and prostate cancer: a new frontier?

Alessandra Modena, Chiara Ciccarese, Roberto Iacovelli, Matteo Brunelli, Rodolfo Montironi, Michelangelo Fiorentino, Giampaolo Tortora, Francesco Massari
  • Alessandra Modena
    Medical Oncology, University-Hospital of Verona, Verona, Italy
  • Chiara Ciccarese
    Medical Oncology, University-Hospital of Verona, Verona, Italy
  • Roberto Iacovelli
    Medical Oncology, University-Hospital of Verona, Verona, Italy
  • Matteo Brunelli
    Department of Pathology and Diagnostic, University-Hospital of Verona, Verona, Italy
  • Rodolfo Montironi
    Section of Pathological Anatomy, Polytechnic University of Marche Region, School of Medicine, Ancona, Italy
  • Michelangelo Fiorentino
    Pathology Service, Addarii Institute of Oncology, S. Orsola-Malpighi Hospital, Bologna, Italy
  • Giampaolo Tortora
    Medical Oncology, University-Hospital of Verona, Verona, Italy
  • Francesco Massari
    Division of Oncology, S. Orsola-Malpighi Hospital, Bologna, Italy | fmassari79@gmail.com

Abstract

Despite recent advances in the treatment of metastatic castrationresistant 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.

Keywords

Prostate cancer; immunotherapy; immune checkpoint inhibitors; CTLA-4; PD-1; PD-L1.

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Submitted: 2016-03-01 15:21:07
Published: 2016-04-15 10:14:41
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Copyright (c) 2016 Alessandra Modena, Chiara Ciccarese, Roberto Iacovelli, Matteo Brunelli, Rodolfo Montironi, Michelangelo Fiorentino, Giampaolo Tortora, Francesco Massari

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