Wen Hui, Zheng Shi, Zhu Xiaoqin, Wang Ling, Chen Dongping
Department of Nephrology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Traditional Chinese Medicine (TCM) Institute of Kidney Disease of Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Front Immunol. 2025 Sep 2;16:1643533. doi: 10.3389/fimmu.2025.1643533. eCollection 2025.
Renal cell carcinoma (RCC) is a highly vascularized and immunogenic malignancy with a complex tumor microenvironment (TME) that shapes disease progression and therapeutic resistance. Despite advances in immune checkpoint inhibitors (ICIs) and targeted therapies, clinical responses remain heterogeneous, underscoring the need for a deeper understanding of RCC immunobiology. This review comprehensively examines the immunosuppressive TME of RCC, emphasizing the roles of cytotoxic and immunosuppressive immune cells, carcinoma-associated fibroblasts (CAFs), abnormal vasculature, and extracellular matrix (ECM) remodeling in fostering immune evasion. This review summarized emerging biomarkers-including PD-L1 expression, tumor mutational burden (TMB), gene mutations, and immune-based subtypes-that may predict ICI response. Furthermore, we evaluate current immunotherapeutic strategies, such as ICIs, combination therapies, and novel approaches targeting immunosuppressive cells and metabolic pathways. While combination therapies have improved outcomes, challenges like toxicity and resistance persist, necessitating biomarker-driven patient stratification and optimized treatment sequencing. Future directions should focus on deciphering TME heterogeneity and developing precision immunotherapy strategies to enhance clinical efficacy in RCC.
肾细胞癌（RCC）是一种血管高度丰富且具有免疫原性的恶性肿瘤，其肿瘤微环境（TME）复杂，影响疾病进展和治疗耐药性。尽管免疫检查点抑制剂（ICI）和靶向治疗取得了进展，但临床反应仍然存在异质性，这凸显了深入了解RCC免疫生物学的必要性。本综述全面研究了RCC的免疫抑制性TME，强调了细胞毒性和免疫抑制性免疫细胞、癌相关成纤维细胞（CAF）、异常血管和细胞外基质（ECM）重塑在促进免疫逃逸中的作用。本综述总结了新兴的生物标志物，包括程序性死亡受体1配体（PD-L1）表达、肿瘤突变负荷（TMB）、基因突变和免疫亚型，这些可能预测ICI反应。此外，我们评估了当前的免疫治疗策略，如ICI、联合治疗以及针对免疫抑制细胞和代谢途径的新方法。虽然联合治疗改善了治疗效果，但毒性和耐药性等挑战仍然存在，因此需要基于生物标志物的患者分层和优化治疗顺序。未来的方向应集中在解读TME异质性和制定精准免疫治疗策略，以提高RCC的临床疗效。
