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重新审视免疫疗法:聚焦前列腺癌。

Revisiting Immunotherapy: A Focus on Prostate Cancer.

机构信息

Department of Pathology, The University of Alabama at Birmingham, Birmingham, Alabama.

McWhorter School of Pharmacy, Samford University, Birmingham, Alabama.

出版信息

Cancer Res. 2020 Apr 15;80(8):1615-1623. doi: 10.1158/0008-5472.CAN-19-2948. Epub 2020 Feb 17.

Abstract

Therapeutic interventions to harness the immune system against tumor cells have provided mixed results in the past for several solid tumors and hematologic malignancies. However, immunotherapy has advanced considerably over the last decade and is becoming an integral combination for treating patients with advanced solid tumors. In particular, prostate cancer immunotherapy has shown modest efficacy for patients in the past. With several key discoveries on immune mechanisms and advanced molecular diagnostic platforms recently, immunotherapy is re-emerging as a viable option for prostate cancer, especially castration-resistant prostate cancer (CRPC), to stimulate antitumor immunity. Combination of patient-tailored immunotherapy and immune checkpoint blockers with conventional cytotoxic agents and androgen receptor-targeted therapies should move the field forward. With a recent adaptation that the application of immune checkpoint inhibitors has been successful in the treatment of more than a dozen solid tumors, including melanoma, lymphoma, liver, cervical, gastrointestinal, and breast cancers, it is a timely endeavor to harness immunotherapy for prostate cancer. Here, we provide an account on the progression of immunotherapy with new discoveries and precision approaches for tumors, in particular CRPC, from mechanistic standpoint to emerging limitations and future directions.

摘要

过去,针对多种实体瘤和血液恶性肿瘤,利用免疫系统对抗肿瘤细胞的治疗干预措施的效果喜忧参半。然而,免疫疗法在过去十年中取得了重大进展,已成为治疗晚期实体瘤患者的重要联合治疗方法。特别是,前列腺癌免疫疗法过去曾为患者带来一定的疗效。最近在免疫机制和先进的分子诊断平台方面的几项关键发现使免疫疗法重新成为治疗前列腺癌(尤其是去势抵抗性前列腺癌)的可行选择,以刺激抗肿瘤免疫。将个体化免疫疗法与免疫检查点抑制剂与传统细胞毒性药物和雄激素受体靶向治疗相结合,应能推动该领域的发展。最近的一项发现表明,免疫检查点抑制剂在治疗包括黑色素瘤、淋巴瘤、肝癌、宫颈癌、胃肠道癌和乳腺癌在内的十多种实体瘤方面取得了成功,因此及时将免疫疗法应用于前列腺癌是很有必要的。在这里,我们从机制角度介绍了免疫疗法在肿瘤(特别是去势抵抗性前列腺癌)方面的新发现和精准方法的进展,并探讨了其目前的局限性和未来的发展方向。

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