Movassaghi Miyad, Chung Rainjade, Anderson Christopher B, Stein Mark, Saenger Yvonne, Faiena Izak
Department of Urology, Columbia University Irving Medical Center, New York, NY 10032, USA.
Department of Medicine, Division of Medical Oncology, Columbia University Irving Medical Center, New York, NY 10032, USA.
Cancers (Basel). 2021 Sep 23;13(19):4757. doi: 10.3390/cancers13194757.
The use of immunotherapy has become a critical treatment modality in many advanced cancers. However, immunotherapy in prostate cancer has not been met with similar success. Multiple interrelated mechanisms, such as low tumor mutational burden, immunosuppressive cells, and impaired cellular immunity, appear to subvert the immune system, creating an immunosuppressive tumor microenvironment and leading to lower treatment efficacy in advanced prostate cancer. The lethality of metastatic castrate-resistant prostate cancer is driven by the lack of therapeutic regimens capable of generating durable responses. Multiple strategies are currently being tested to overcome immune resistance including combining various classes of treatment modalities. Several completed and ongoing trials have shown that combining vaccines or checkpoint inhibitors with hormonal therapy, radiotherapy, antibody-drug conjugates, chimeric antigen receptor T cell therapy, or chemotherapy may enhance immune responses and induce long-lasting clinical responses without significant toxicity. Here, we review the current state of immunotherapy for prostate cancer, as well as tumor-specific mechanisms underlying therapeutic resistance, with a comprehensive look at the current preclinical and clinical immunotherapeutic strategies aimed at overcoming the immunosuppressive tumor microenvironment and impaired cellular immunity that have largely limited the utility of immunotherapy in advanced prostate cancer.
免疫疗法的应用已成为许多晚期癌症的关键治疗方式。然而，前列腺癌的免疫疗法尚未取得类似的成功。多种相互关联的机制，如肿瘤突变负荷低、免疫抑制细胞和细胞免疫受损，似乎会破坏免疫系统，营造出免疫抑制性肿瘤微环境，并导致晚期前列腺癌的治疗效果降低。转移性去势抵抗性前列腺癌的致死性是由缺乏能够产生持久反应的治疗方案所致。目前正在测试多种策略来克服免疫抵抗，包括联合各类治疗方式。多项已完成和正在进行的试验表明，将疫苗或检查点抑制剂与激素疗法、放射疗法、抗体药物偶联物、嵌合抗原受体T细胞疗法或化疗联合使用，可能会增强免疫反应并诱导持久的临床反应，且无明显毒性。在此，我们综述前列腺癌免疫疗法的现状以及治疗抵抗背后的肿瘤特异性机制，全面审视当前旨在克服免疫抑制性肿瘤微环境和细胞免疫受损的临床前和临床免疫治疗策略，这些因素在很大程度上限制了免疫疗法在晚期前列腺癌中的应用。
