UC Irvine

Immunotherapy remains to be an appealing treatment option for prostate cancer with some documented promise. Prostate cancer is traditionally considered as an immunologically "cold" tumor with low tumor mutation burden, low expression of PD-L1, sparse T-cell infiltration, and a immunosuppressive tumor microenvironment (TME). Sipuleucel-T (Provenge) is the first FDA approved immunotherapeutic agent for the treatment of asymptomatic or minimally symptomatic metastatic castrate resistant prostate cancer (mCRPC); demonstrating a benefit in overall survival. However various clinical trials by immune checkpoint inhibitors (ICIs) and their combinations with other drugs have shown limited responses in mCRPC. Up to now, only a small subset of patients with mismatch repair deficiency/microsatellite instability high and CDK12 mutations can clinically benefit from ICIs and/or their combinations with other agents, such as DNA damage agents. The existence of a large heterogeneity in genomic alterations and a complex TME in prostate cancer suggests the need for identifying new immunotherapeutic targets. As well as designing personalized immunotherapy strategies based on patient-specific molecular signatures. There is also a need to adjust strategies to overcome histologic barriers such as tissue hypoxia and dense stroma. The racial differences of immunological responses between men of diverse ethnicities also merit further investigation to improve the efficacy of immunotherapy and better patient selection in prostate cancer.