Immune Response Drives Outcomes in Prostate Cancer: Implications for Immunotherapy

Background The heterogeneity of the immune microenvironment leads to the different response results of immune checkpoint blockade therapy. We aimed to propose a robust molecular classification of prostate cancer microenvironment to identify ideal patients for delivering effective immunotherapy. Methods A total of 1,557 prostate cancer patients were enrolled in the current study, including 69 real-world samples from the AHMU-PC cohort. Non-negative matrix factorization algorithm was employed to virtually microdissect the patients to immune and non-immune subclasses. The patients in the immune class were dichotomized to immune activated and suppressed subtypes by the nearest template prediction of activated stroma signature. The curative effects of different immune subclasses in response to immunotherapy were also predicted. Results We termed the newly identified molecular class of tumors as “immune class”, which was characterized by a high enrichment of T cell, B cell, NK cell, macrophage associated signatures, etc. , compared with the non-immune class (all, P < 0.05). Subsequently, the immune class was subclassified into immune activated and suppressed subtypes determined by the activation status of WNT/TGF-β, TGF-β1, and C-ECM signatures. As a result, around 14.9% to 24.3% of overall patients belonged to the immune activated subgroup, and they were proved with the favorable recurrence-free survival outcomes than others and showed potential curative effects in response to the anti-PD-1/PD-L1 immunotherapy. Conclusion Our study identifies a novel immune class in prostate cancer, which is further described by active or exhausted immune responses. These findings provide novel insights into tailoring immunotherapeutic strategies for different prostate cancer subgroups. Highlights ▪ Immunotherapy could trigger a durable response in advanced prostate cancer, but it only benefits a minority of patients; ▪ Immune response drives recurrence-free survival outcomes in prostate cancer; ▪ The robust molecular classification system helps identify more ideal patients for delivering anti-PD-1/PD-L1 immunotherapy.