Beyond conventional immune-checkpoint inhibition - novel immunotherapies for renal cell carcinoma.
Beyond conventional immune-checkpoint inhibition - novel immunotherapies for renal cell carcinoma.
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DOI：
10.1038/s41571-020-00455-z
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发表时间：
2021-04
期刊：
影响因子：
--
通讯作者：
Choueiri TK
中科院分区：
文献类型：
--
作者：
Braun DA;Bakouny Z;Hirsch L;Flippot R;Van Allen EM;Wu CJ;Choueiri TK
免疫检查点抑制剂（ICI）的发展改变了晚期肾细胞癌（RCC）的管理，但大多数RCC患者仍然没有获得持久的临床益处。重要的是，RCC与其他免疫治疗反应性实体瘤有很大不同-它具有适度的突变负荷，矛盾的是，高CD 8 + T细胞浸润与预后较差相关。基于靶向PD-1和CTLA-4轴的抑制性抗体的成功，目前正在临床开发多种创新的免疫疗法用于治疗RCC，包括新的ICI、共刺激通路激动剂、修饰的细胞因子、代谢通路调节剂、细胞疗法和治疗性疫苗。然而，成功开发这种新型的基于免疫的治疗和基于免疫治疗的组合将需要一个RCC特异性框架，以了解作为有效抗肿瘤免疫应答基础的必要免疫干预。在这里，使用由良好描述的癌症免疫循环提供的结构，我们概述了成功的抗RCC免疫应答所需的关键步骤，并描述了在此框架内有前途的新免疫疗法的发展。通过这种方法，我们总结和分析了RCC微环境中令人鼓舞的靶点，并回顾了这种疾病的抗原导向治疗的前景。
The management of advanced renal cell carcinoma (RCC) has been transformed by the development of immune checkpoint inhibitors (ICIs), but still most RCC patients do not receive durable clinical benefit. Importantly, RCC differs substantially from other immunotherapy-responsive solid tumors – it has a modest mutation burden, and paradoxically, high CD8+ T cell infiltration has been associated with a worse prognosis. Building on the successes of inhibitory antibodies targeting the PD-1 and CTLA-4 axes, multiple innovative immunotherapies are now in clinical development for the treatment of RCC, including new ICIs, co-stimulatory pathway agonists, modified cytokines, metabolic pathway modulators, cellular therapies, and therapeutic vaccinations. However, the successful development of such novel immune-based treatments and of immunotherapy-based combinations will require a RCC-specific framework for understanding the necessary immunotherapeutic interventions that underlie an effective anti-tumor immune response. Here, using the structure provided by the well-described cancer-immunity cycle, we outline the key steps required for a successful anti-RCC immune response, and describe the development of promising new immunotherapies within the context of this framework. With this approach, we summarize and analyze encouraging targets within the RCC microenvironment, and review the landscape of antigen-directed therapies in this disease.
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影响因子：
82.9
作者：
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