Immunogenomic analysis of advanced prostate cancer has identified immunological alterations associated with defective mismatch repair (dMMR) that could inform immunotherapy strategies. Overall, dMMR status was confirmed in 8.1% of patients and was associated with poor overall survival; dMMR tumours with high microsatellite instability (MSI) had increased mutational load, T cell infiltration, and PD-L1 expression. Interestingly, dMMR mutational signatures positively correlated with MSI and expression of immune-associated genes, including PDL1 and PDL2.