Immunotherapy of Prostate Cancer: Facts and Hopes

Abstract

In the last few years, immunotherapy has become an important cancer treatment modality, and although the principles of immunotherapy have evolved over many decades, the FDA approvals of sipuleucel-T and ipilimumab began a new wave in immuno-oncology. Despite the current enthusiasm, it is unlikely that any of the immunotherapeutics alone can dramatically change prostate cancer outcomes, but combination strategies are more promising and provide a reason for optimism. Several completed and ongoing studies have shown that the combination of cancer vaccines or checkpoint inhibitors with different immunotherapeutic agents, hormonal therapy (enzalutamide), radiotherapy (radium 223), DNA-damaging agents (olaparib), or chemotherapy (docetaxel) can enhance immune responses and induce more dramatic, long-lasting clinical responses without significant toxicity. The goal of prostate cancer immunotherapy does not have to be complete eradication of advanced disease but rather the return to an immunologic equilibrium with an indolent disease state. In addition to determining the optimal combination of treatment regimens, efforts are also ongoing to discover biomarkers of immune response. With such concerted efforts, the future of immunotherapy in prostate cancer looks brighter than ever. Clin Cancer Res; 23(22); 6764-70. ©2017 AACR.

Figure 1. Requirements for effective immunotherapy

A) Generation of immune response. Antigen-presenting cells process targeted antigens (green) and present them to T cells with major histocompatibility complexes (MHC) on their surface, along with costimulatory molecules. This complex stimulates T cells to become cytotoxic CD8⁺ T cells. B) Functional effector cells within the tumor. Activated cytotoxic T cells recognize targeted antigens on the surface of cancer cells and release cytotoxins such as perforin and granzymes, triggering caspases and apoptosis. In addition, activated T cells also express Fas ligands that bind to Fas receptors on tumor cells, also inducing apoptosis.