ABSTRACT
Although immunotherapy has revolutionized cancer treatment and achieved remarkable success across many different cancer types, only a subset of patients shows meaningful clinical responses. In particular, advanced prostate cancer exhibits overwhelming de novo resistance to immune checkpoint blockade therapy. This is primarily due to the immunosuppressive tumor microenvironment of prostate cancer. Therefore, it is paramount to understand how prostate cancer cell-intrinsic mechanisms promote immune evasion and foster an immunosuppressive microenvironment. Here, we review recent findings that reveal the roles of the genetic alterations, androgen receptor signaling, cancer cell plasticity, and oncogenic pathways in shaping the immunosuppressive microenvironment and thereby driving immunotherapy resistance. Based on preclinical and clinical observations, a variety of therapeutic strategies are being developed that may illuminate new paths to enhance immunotherapy efficacy in prostate cancer.
Subject(s)
Male , Humans , Prostatic Neoplasms/pathology , Prostate/pathology , Immunotherapy , Tumor MicroenvironmentABSTRACT
Patients with castration-resistant prostate cancer (CRPC) who received a novel androgen receptor pathway inhibitor (ARPI) often show drug resistance in response to treatment. Tumors acquire androgen receptor (AR)-independent subtypes, so that cancer cells no longer depend on AR pathway to continue to grow. More and more studies have shown that after CRPC patients received ARPI treatment, some patients not only failed to achieve the clinical benefit but also experienced the evolution of tumor progression, that is, neuroendocrine prostate cancer (NEPC). NEPC is closely related to poor prognosis. So far, rare effective and reliable drugs have been found clinically to treat NEPC. This article aims to summarize the mechanism of NEPC and the molecular targets, and provide references for the diagnosis and treatment of NEPC patients.