Abstract:

With the rapid development of cancer immunology, more and more research focuses on the role of immune cells and signaling molecules in the tumor microenvironment. Prostate cancer is the second most common malignant tumor in men globally. With the increase in our population ages and screening rates, the incidence of prostate cancer in China is increasing. Androgen deprivation therapy (ADT) is a primary treatment for late-stage prostate cancer. However, most patients eventually progress to castration-resistant prostate cancer (CRPC) after ADT treatment. The median survival of CRPC patients has been less than two years. Although new treatment methods have emerged in recent years, and patient survival has improved, however, the overall prognosis still remains poor. Tumor immunotherapy works by stimulating or rebuilding the body's immune system to control and kill tumor cells. In recent years, immunotherapy has entered clinical research and rapidly developed into an effective tumor-treatment approach following surgery, radiotherapy, chemotherapy and targeted therapy. However, the effect of immunotherapy on CRPC patients is usually very poor. Therefore, the tumor microenvironment of CRPC has attracted many scholars' attention. Previous studies have suggested that CRPC generally has less immune infiltration, a relatively high immunosuppressive tumor microenvironment, such as low infiltration and activity of T cells, and high expressions of various immunosuppressive factors, such as cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1), etc., which is considered as an immune "cold" tumor. In addition to its own immune-inhibitory mechanisms, CRPC has complex immune evasion mechanisms that suppress immune cell activity or selectively express low immunogenic antigen to evade immune system recognition. Due to the particular immunosuppressive tumor microenvironment of CRPC, the effect of immunotherapy alone is often unsatisfactory. Therefore, the selection of appropriate immunotherapy strategies has become the key to improving the treatment effect of CRPC patients. This review summarized the mechanisms underlying immune cells in the immune microenvironment of CRPC tumors and their interactions with various cytokines in the context of immune checkpoint inhibitor therapy combined with ADT, chemotherapy, Sipuleucel-T tumor vaccines, chimeric antigen receptor-T (CAR-T) cell therapy, oncolytic virus therapy, or in combination with chemokine receptor antagonists, tyrosine kinase inhibitors, poly (ADP-ribose) polymerase (PARP) inhibitors and other treatments. In conclusion, the tumor immune microenvironment of CRPC is highly complex, and immunotherapy still faces many challenges. However, with the progress of technological advancements and research, some new immunotherapy options are being studied, and it is believed that tumor immunotherapy will bring better therapeutic effects to patients with CRPC in the future.

Key words: Castration-resistant, Prostate cancer, Tumor immune microenvironment