Prostate Cancer Immunotherapy-Finally in From the Cold?

Abstract

Purpose of review: Despite significant progress, patients with metastatic prostate cancer continue to have poor prognosis. Immunotherapy has revolutionized cancer care for many tumor types but has a limited role in the treatment of prostate cancer. This review discusses the promise of immunotherapy in prostate cancer treatment with an emphasis on emerging therapeutic targets.

Recent findings: Most prostate tumors have low tumor mutational burden and lack immunogenicity, representing significant hurdles to induction of anti-tumor immunity. However, recent research centered on deciphering key mechanisms of immune resistance in the prostate tumor microenvironment has led to the discovery of a range of new treatment targets. These discoveries are currently being translated into innovative immunotherapy clinical trials for patients with prostate cancer. Recent progress includes early evidence of activity for these novel approaches and the identification of potential predictive biomarkers of response. Novel treatment strategies using new antigen-directed therapies, drugs targeting the immunosuppressive tumor microenvironment, and combination immunotherapy therapies show great potential and are currently in clinical development. In addition, a deeper understanding of predictors of response and resistance to immunotherapy in prostate cancer is allowing for a more personalized approach to therapy.

Keywords: Antibody-drug conjugates; Bispecific antibodies; Cancer vaccines; Cell signaling pathways; Chimeric antigen receptor T-cells (CAR T-cells); Cytokine inhibition; Immune checkpoint inhibition; Immunotherapy; Interleukin-8; Metastatic castration-resistant prostate cancer; Prostate cancer; Prostate stem cell antigen; Prostate-specific antigen; Prostate-specific membrane antigen; Prostatic acid phosphatase; Six transmembrane epithelial antigen of the prostate 1; Transforming growth factor beta (TGF-β); Tumor microenvironment.