Prostate Cancer Therapy via Inhibition of Negative Immune Regulation

Prostate cancer exhibits complex pathophysiology, rendering its management arduous due to heterogeneity and recalcitrance toward conventional therapeutics. The increasing focus on immune checkpoint inhibitors for treatment stems from the limited existing therapeutic approaches and the impressive effectiveness of these inhibitors demonstrated in other malignancies. Denoted as immunologically "cold" with low tumor mutation burden (TMB), prostate cancer manifests diminished immune cell infiltration in tumoral tissue, potentially culminating in inadequate response to immune checkpoint blockade. Nonetheless, a substantial proportion of metastatic castration-resistant prostate cancer (mCRPC) patients bear germline or somatic mutations in DNA repair genes, such as BReast CAncer gene 2 (BRCA2) and ataxia telangiectasia mutated (ATM), potentially augmenting TMB and neoantigen load, thus potentially prognosticating immunotherapy responsiveness. Complete immune response activation necessitates supplementary proteins functioning as T-cell accelerators or inhibitors, such as cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1). Immune checkpoint inhibitors were thus developed, occluding negative regulatory pathways exploited by neoplastic cells to elude the immune system. Although clinical trials appear promising, proper patient selection and surveillance are imperative due to potential immune-related adverse events. As the field progresses, immune checkpoint inhibitors are anticipated to constitute an increasingly integral facet of the therapeutic armamentarium for prostate cancer.