Neoantigen responses to Immunotherapy in Prostate Cancer

To determine whether antigen-specific T cell responses can be elicited following treatment with ICT in cancers that have a low TMB, a clinical trial with ipilimumab (anti-CTLA-4) was conducted in 30 patients with metastatic castration-resistant prostate cancer (CRPC). We identified 2 distinct groups of patients divided by clinical outcomes, which consisted of a cohort with Favorable and Unfavorable outcomes. Compared to the Unfavorable cohort, the patients in the Favorable cohort were more likely to have higher intratumoral CD8 T cell density and/or IFN-γ response gene signature, including five patients who had antigen-specific T cell responses that were only detectable after ipilimumab therapy. Three patients had T cell responses against tumor-associated antigens (PSMA and PAP). Importantly, two patients with a relatively low TMB had T cell responses against unique neoantigens. Collectively, our data indicate that a subset of patients with metastatic prostate cancer benefit from ICTs, particularly those who have immunological biomarkers associated with effector T cell responses.EGA study EGAS00001004050