Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
Medicine, Weill Cornell Medical College, New York, USA.
Expert Opin Biol Ther. 2020 May;20(5):481-487. doi: 10.1080/14712598.2020.1735345. Epub 2020 Mar 5.
: Within the last decade, multiple innovative immune platforms have been developed and tested in patients with metastatic castration-resistant prostate cancer (mCRPC) with only one demonstrating a survival benefit. The advent of immunogenomics along with the availability of diverse checkpoint inhibitors provides inroads in treating these patients, in many cases with significant clinical impact but unfortunately not in all patients. How to exploit these novel platforms remains an area of increased interest especially in the setting of new agents that can affect the tumor microenvironment and potentially render a 'cold' tumor to become 'hot.': This review highlights the current changes and challenges in this field and how to best use our current knowledge for better trial designs in patients with mCRPC.: Recent understanding of the inhibitory milieu within the tumor microenvironment has fostered the use of combinatorial strategies that target not only tumor cells but capitalize on controlling inhibitory cell populations and cytokines that induce a hostile setting for immune cells. Immunogenomics and genomic interrogation of prostate cancers have opened a vista as to how patients' tumors that can respond to immune agents that previously were thought have minimal antitumor activity.
: 在过去的十年中,已经开发并测试了多种创新的免疫平台,用于治疗转移性去势抵抗性前列腺癌(mCRPC)患者,其中只有一种显示出了生存获益。免疫基因组学的出现以及多种检查点抑制剂的应用为治疗这些患者提供了途径,在许多情况下具有显著的临床影响,但不幸的是并非所有患者都受益。如何利用这些新平台仍然是一个日益关注的领域,特别是在新的药物可以影响肿瘤微环境并可能使“冷肿瘤”变为“热肿瘤”的情况下。: 这篇综述强调了该领域的当前变化和挑战,以及如何最好地利用我们现有的知识,为 mCRPC 患者的更好的临床试验设计提供指导。: 最近对肿瘤微环境中抑制性环境的理解促进了联合策略的使用,这些策略不仅针对肿瘤细胞,还利用控制抑制性细胞群和细胞因子的方法,为免疫细胞创造一个有利的环境。免疫基因组学和前列腺癌的基因组研究揭示了一种可能性,即以前认为具有最小抗肿瘤活性的免疫药物如何能够使某些患者的肿瘤产生应答。