肾细胞癌（RCC），尤其是透明细胞肾细胞癌，通常被认为是一种免疫治疗敏感的癌症。最近，随着基于抗PD-1/PD-L1/CTLA-4免疫检查点抑制剂（ICI）的治疗方案的监管批准，局部晚期和转移性肾细胞癌患者的预后显着改善。然而，在大多数情况下，肾细胞癌最初对治疗仍无反应，或者随着时间的推移会产生耐药性。因此，了解导致 ICI 耐药的原因并开发新型免疫和非免疫治疗以增强对 ICI 的反应仍然是一个未满足的需求。在这篇综述中，我们重点介绍了最近发表的研究和最新的临床研究，这些研究调查了传统 ICI 之外的局部晚期和转移性 RCC 的下一代免疫方法。这些试验包括细胞因子、基于肠道微生物群的疗法、新型免疫检查点药物、疫苗和嵌合抗原受体 T 细胞。这些药物作为单一疗法或与传统 ICI 联合疗法正在接受评估，有望很快为 RCC 患者带来更好的治疗效果。

Renal cell carcinoma (RCC), especially clear cell RCC, is generally considered an immunotherapy-responsive cancer. Recently, the prognosis for patients with locally advanced and metastatic RCC has significantly improved with the regulatory approvals of anti-PD-1/PD-L1/CTLA-4 immune checkpoint inhibitor (ICI)-based regimens. Yet in most cases, RCC will remain initially unresponsive to treatment or will develop resistance over time. Hence, there remains an unmet need to understand what leads to ICI resistance and to develop novel immune and nonimmune treatments to enhance the response to ICIs. In this review, we highlight recently published studies and the latest clinical studies investigating the next generation of immune approaches to locally advanced and metastatic RCC beyond traditional ICIs. These trials include cytokines, gut microbiota-based therapies, novel immune checkpoint agents, vaccines, and chimeric antigen receptor T cells. These agents are being evaluated as monotherapy or in combination with traditional ICIs and will hopefully provide improved outcomes to patients with RCC soon.