Immune response drives outcomes in prostate cancer: implications for immunotherapy

The heterogeneity of the immune microenvironment leads to different responses in immune checkpoint blockade therapy. We aimed to propose a robust molecular classification system to investigate the relevance of the immune microenvironment subtype and prognosis of prostate cancer patients, as well as the therapeutic response to immune checkpoint blockade therapy. A total of 1,557 prostate cancer patients were enrolled, including 69 real‐world samples from our institute (titled the AHMU‐PC cohort). The non‐negative matrix factorization algorithm was employed to virtually microdissect patients. The immune enrichment was characterized by a high enrichment of T cell‐, B cell‐, NK cell‐, and macrophage‐associated signatures, by which patients were subclassified into nonimmune and immune classes. Subsequently, the immune class was dichotomized into immune‐activated and immune‐suppressed subtypes based on the stromal signature, represented by the activation of WNT/TGF‐β, TGF‐β1, and C‐ECM signatures. Approximately 14.9% to 24.3% of patients belonged to the immune‐activated subtype, which was associated with favorable recurrence‐free survival outcomes. In addition, patients in the immune‐activated subtype were predicted to benefit more from anti‐PD‐1/PD‐L1 therapy. In conclusion, our study identifies a novel immune molecular classifier that is closely related to clinical prognosis and provides novel insights into immunotherapeutic strategies for prostate cancer patients. This study identifies a novel immune molecular classifier for prostate cancer based on the analysis of 1,557 cases. Patients in the immune activated subgroup were associated with favorable prognosis and better outcomes of anti‐PD‐1/PD‐L1 therapy. Our findings suggest that the immune response drives clinical outcomes in prostate cancer, highlighting important implications for immunotherapy in patients with prostate cancer.