The evolving landscape of immunotherapy in advanced prostate cancer

Abstract

Prostate cancer exists in a clinical continuum of hormone-sensitive to castration-resistant disease. Despite the use of chemotherapy and androgen synthesis inhibitors in the castration-resistant setting, this remains a lethal disease. The advent of immune checkpoint blockade has changed the outlook for cancer treatment and survival for several tumors since its first approval in 2011; however, the clinical benefit in castration-resistant prostate cancer (CRPC) is rather limited. Currently, Sipuleucel-T remains the only immune modality to be approved in CRPC setting. Such immune resistance likely exists due to low immunogenicity of prostate tumor cells and an immunosuppressive tumor microenvironment. In this review, we describe the early experiences of immune checkpoint blockade and therapeutic vaccines in CRPC. We then outline strategies currently being implemented to overcome immune resistance, as well as genomic biomarker investigation to identify patients that may harbor more immunogenic tumors. At last, we preview emerging immunotherapeutic platforms.