The recent discovery of immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment, including the treatment for renal cell carcinoma (RCC). Following the eras of cytokines and molecularly targeted therapies including vascular endothelial growth factor–directed agents and mammalian target of rapamycin (mTOR) inhibitors, ICIs have become the latest addition to the RCC armamentarium. To understand the scientific rationale behind this revolution in RCC treatment, we have reviewed the fundamental discoveries underlying the transition from old (cytokines) to new (ICIs) immunotherapies. We summarize the pivotal trials (CheckMate 025, CheckMate 214, KEYNOTE-426, JAVELIN Renal 101, IMmotion151) of checkpoint inhibitors for clear cell RCC in various treatment settings. With the availability of many different combination therapies and many more currently under investigation, clear cell RCC treatment is becoming more complex. Patient preferences, disease volumes, and adverse event profiles are essential in determining which option is the best for an individual patient. In the future, biomarkers currently under development could guide these treatment decisions.

免疫检查点抑制剂的最新发现(ICIs) 彻底改变了癌症治疗，包括肾细胞癌 (RCC) 的治疗。随着细胞因子和分子靶向疗法（包括血管内皮生长因子导向剂和哺乳动物雷帕霉素靶标 (mTOR) 抑制剂）时代的到来，ICI 已成为 RCC 设备的最新成员。为了理解 RCC 治疗革命背后的科学原理，我们回顾了从旧（细胞因子）到新（ICI）免疫疗法过渡的基本发现。我们总结了在各种治疗环境中用于透明细胞 RCC 的检查点抑制剂的关键试验（CheckMate 025、CheckMate 214、KEYNOTE-426、JAVELIN Renal 101、IMmotion151）。随着许多不同的联合疗法的出现，以及更多目前正在研究中的疗法，透明细胞 RCC 治疗变得越来越复杂。患者偏好、疾病数量和不良事件概况对于确定哪种选择最适合个体患者至关重要。未来，目前正在开发的生物标志物可以指导这些治疗决策。