Despite advances in diagnostic and therapeutic technology, prostate cancer remains a leading cause of morbidity and mortality among men. While androgen deprivation therapy and next-generation androgen receptor pathway inhibitors offer durable responses, the emergence of the lethal phenotype, metastatic castration-resistant prostate cancer (mCRPC) eventually develops for most. A growing body of evidence points to the tumor microenvironment (TME) as a key driver of immune evasion and therapeutic failure. This review focuses on the current knowledge of immune suppression in the prostate TME, including cancer-associated fibroblasts, myeloid-derived suppressor cells, tumor-associated macrophages, immune checkpoint pathways, and several associated key metabolic alterations. These cellular and molecular networks contribute to therapeutic resistance and disease progression and may be used as therapeutic targets. We will also examine emerging treatment strategies aimed at reprogramming the TME, as well as combination approaches incorporating immunotherapies with other signaling inhibitors. Future success in clinical therapeutic development for mCRPC will depend on rational combinations that address both tumor-intrinsic resistance and extrinsic immune suppression, with emphasis on biomarker-driven patient and treatment selection.
尽管诊断与治疗技术不断进步，前列腺癌仍是导致男性发病和死亡的主要原因。虽然雄激素剥夺疗法和新型雄激素受体通路抑制剂能产生持续疗效，但多数患者最终仍会发展为致命表型——转移性去势抵抗性前列腺癌（mCRPC）。越来越多的证据表明，肿瘤微环境（TME）是免疫逃逸和治疗失败的关键驱动因素。本综述聚焦当前对前列腺肿瘤微环境中免疫抑制机制的认识，包括癌症相关成纤维细胞、髓源性抑制细胞、肿瘤相关巨噬细胞、免疫检查点通路及若干关键代谢改变。这些细胞与分子网络共同导致治疗抵抗和疾病进展，并可能成为治疗靶点。我们还将探讨旨在重编程肿瘤微环境的新兴治疗策略，以及免疫疗法与其他信号抑制剂联合应用的组合方案。未来mCRPC临床治疗的成功开发，将取决于能够同时解决肿瘤内在耐药性和外源性免疫抑制的合理联合疗法，并重点关注生物标志物驱动的患者与治疗方案选择。
肿瘤(癌症)患者之家