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Efficacy of Enzalutamide (ENZ) in castration resistant prostate cancer (CRPC) patients is short-lived. Immunotherapy like T cell checkpoint blockade may improve patient survival. However, when and where checkpoint molecules are expressed in CRPC and whether immune evasion is a mechanism of ENZ resistance remains unclear. Thus, we investigated whether clinically relevant immunotherapy targets, specifically PD-L1/2, PD-1 and CTLA-4, are upregulated in ENZ resistant (ENZR) patients and in a pre-clinical model of ENZ resistance. We show for the first time that patients progressing on ENZ had significantly increased PD-L1/2+ dendritic cells (DC) in blood compared to those naïve or responding to treatment, and a high frequency of PD-1+ T cells. These data supported our pre-clinical results, in which we found significantly increased circulating PD-L1/2+ DCs in mice bearing ENZR tumors compared to …