The temporal dynamics of the immune response to neoadjuvant androgen deprivation therapy suggests a window-of-opportunity for checkpoint inhibitor therapy in prostate cancer

Immune Checkpoint inhibitors (CPIs) have not been effective in treating most human prostate cancers. This study describes the temporal dynamics of the immune response of primary prostate cancers to neoadjuvant androgen deprivation therapy (nADT), and suggests a strategic approach to improve the efficacy of CPIs in prostate cancer. After several months of nADT, inflammation and immune-related pathways were activated, accompanied by a robust infiltration of both CD8 ⁺ and CD4 ⁺ T cell into prostate tumors, indicating effector T cell education and activation. In contrast, six or more months nADT leads to an immunosuppressive shift, evidenced by increased M2-like tumor associated macrophages and regulatory T cells. Thus, our findings suggest a critical window of opportunity following nADT for initiating CPIs. This provides a rationale for the precise sequencing of nADT and CPI regimens to maximize therapeutic benefit.