CRISPR/Cas9-mediated deletion of IRE1α or treatment with its small molecule inhibitor MKC8866 (ORIN1001), which is currently in clinical trials, reprogrammed the TME, reversed immunosuppression, increased NK and CD8+ T-cell infiltration, augmented interferon responses, and enhanced the efficacy of anti-PD-1 therapy in various PCa syngeneic mouse models 186. The gene discussed is PDCD1; the disease is posterior cortical atrophy.