肾癌免疫微环境与PD-1/PD-L1免疫治疗研究现状

Research Status of the Immune Microenvironment in Renal Cell Carcinoma and PD-1/PD-L1 Immunotherapy

摘要: 肾癌是全球常见恶性肿瘤，发病率和死亡率呈上升趋势。手术治疗在局限性肾癌中效果较好，但晚期或转移性肾癌的传统治疗方法面临挑战。近年来，免疫治疗在肾癌治疗中取得了进展。本综述从肾癌的微环境与免疫治疗两方面深入探讨。肾癌组织中存在多种免疫细胞浸润，其分布和功能状态对肾癌进展和预后有重要影响。肾癌细胞通过多种方式实现免疫逃逸，如改变细胞表面抗原表达、分泌免疫抑制性细胞因子等。PD-1/PD-L1通路在肾癌中异常激活，其表达调控机制多样，PD-L1高表达会抑制T细胞功能，促进肿瘤免疫逃逸。PD-1/PD-L1免疫检查点抑制剂可阻断该通路，恢复T细胞功能，激活免疫系统产生免疫记忆反应，但应用中存在缺乏有效的预测生物标志物、免疫介导毒性反应等问题。抗血管生成的酪氨酸激酶抑制剂有免疫调节效应，可增强抗PD-1治疗疗效。免疫治疗联合方案在转移性透明细胞肾癌患者中的疗效优于标准一线VEGFR靶向治疗，有望成新标准。新型免疫治疗手段如免疫恢复型CAR-T细胞、新型PD-L1抗体H1A等研究也取得了初步成果。未来需深入解析肾癌免疫微环境的复杂性，开发有效的预测生物标志物，实现个体化治疗方案的精准制定，关注免疫治疗的长期疗效和安全性，优化联合治疗方案，克服免疫耐药，以提高患者的生存率和生活质量。

Abstract: Renal Cell Carcinoma (RCC) is a common malignant tumor worldwide, with increasing incidence and mortality rates. Surgical treatment shows good efficacy in localized RCC, but traditional therapies for advanced or metastatic RCC face significant challenges. In recent years, immunotherapy has made remarkable progress in RCC treatment. This review deeply explores the immune microenvironment of RCC and immunotherapeutic strategies. Multiple immune cells infiltrate RCC tissues, and their distribution and functional status significantly impact RCC progression and prognosis. RCC cells evade immunity through various mechanisms, including altering cell surface antigen expression and secreting immunosuppressive cytokines. The PD-1/PD-L1 pathway is aberrantly activated in RCC, regulated by diverse mechanisms. High PD-L1 expression inhibits T cell function and promotes tumor immune escape. PD-1/PD-L1 Immune Checkpoint Inhibitors (ICIs) block this pathway, restore T cell function, and activate immune memory responses. However, challenges remain, such as the lack of effective predictive biomarkers and immune-mediated toxicities. Antiangiogenic Tyrosine Kinase Inhibitors (TKIs) exhibit immunomodulatory effects, enhancing the efficacy of anti-PD-1 therapy. Combination immunotherapy regimens have shown superior efficacy to standard first-line VEGFR-targeted therapy in metastatic clear cell RCC, emerging as potential new standards. Novel immunotherapies, including immune-restoring CAR-T cells and the PD-L1 antibody H1A, have also achieved preliminary breakthroughs. Future research should focus on deciphering the complexity of the RCC immune microenvironment, developing effective predictive biomarkers, implementing precision personalized therapy, evaluating the long-term efficacy and safety of immunotherapies, optimizing combination regimens, and overcoming immune resistance to improve patient survival and quality of life.