Selective estrogen receptor modulators contribute to prostate cancer treatment by regulating the tumor immune microenvironment

Prostate cancer (PC) has previously been established as a cold tumor and develops in an inert immunosuppressive environment. Current research focuses on altering the immune microenvironment of PC from cold to hot; thus, in the present review, the diverse roles of estrogen and estrogen receptor (ER) signaling was examined in the tumor cell and tumor immune microenvironment (TIM). We hypothesized that ERα promotes PC progression and ERβ impedes epithelial-mesenchymal transition in PC cells, while in the TIM, ERβ mediates the immunosuppressive environment, and low levels of ERα is associated with disease development. Selective estrogen receptor modulators (SERMs) or selective ER degraders play diverse roles in the regulation of ER isoforms. Patients with PC may benefit from the use of SERMs, including raloxifene, in combination with anti-PD1/PD-L1 checkpoint immunotherapy, or TGF-β or Wnt antagonists. The present review demonstrated that immunotherapy-based strategies combined with SERMs may be an option for the future of PC-targeting therapy.