Targeting androgen receptor signaling to enhance cancer immunotherapy.

Men experience higher cancer incidence and mortality than women, and accumulating evidence implicates androgen receptor (AR) signaling as a key biological driver of these sex-based disparities. AR signaling can suppress adaptive anticancer immunity. Preclinical studies across multiple cancer types show that AR inhibition enhances T cell function and sensitizes tumors to immune checkpoint inhibition. However, recent Phase 3 trials combining AR suppression with immune checkpoint blockade in prostate cancer (PCa) failed to demonstrate clinical benefit. We discuss these developments and summarize recent studies defining the role of AR signaling in anticancer immunity. We propose strategies to translate emerging insights into rational trial designs that optimize the integration of AR suppression with immunotherapy.