血管生成和免疫抑制是密切相关的病理生理过程。VEGF信号通路抑制剂被广泛应用于恶性肿瘤和增殖性视网膜病变中，但也可能在某些患者中引发高血压和肾损伤，表现为蛋白尿、肾病综合征、肾功能衰竭和微血管性血栓性疾病。VEGF信号通路抑制剂阻断了VEGF-A和VEGF-C的作用。然而，足细胞产生的VEGF-A和VEGF-C对维持肾小球内皮细胞和足细胞的生理功能至关重要。目前对于与VEGF信号通路抑制剂相关的肾脏疾病仍然没有有效的治疗方法，一些患者即使停药后仍出现进行性肾功能衰竭。最近的研究发现，阻断VEGF-A和VEGF-C可以激活CD4+和CD8+ T细胞，增强树突状细胞的抗原呈递功能，增强巨噬细胞的细胞毒作用，并启动补体级联反应。VEGF和VEGFR在免疫细胞中表达，参与免疫抑制和免疫细胞之间的相互作用。本综述总结了VEGF-A和VEGF-C在肾脏中的表达和功能。还回顾了目前关于VEGF信号通路抑制剂的免疫调节机制。最后，总结了联合策略，以突出VEGF信号通路抑制剂的提议。版权所有© 2023。Elsevier公司出版。

Angiogenesis and immunosuppression are closely related pathophysiologic processes. Widely prescribed in malignant tumor and proliferative retinal lesions, VEGF signaling pathway inhibitors may cause hypertension and renal injury in some patients, presenting with proteinuria, nephrotic syndrome, renal failure and thrombotic microangiopathy. VEGF signaling pathway inhibitors block the action of both VEGF-A and VEGF-C. However, VEGF-A and VEGF-C produced by podocytes are vital to maintain the physiological function of glomerular endothelial cells and podocytes. There is still no effective treatment for kidney disease associated with VEGF signaling pathway inhibitors and some patients have progressive renal failure even after withdrawal of the drug. Recent studies reveal that blocking of VEGF-A and VEGF-C can activate CD4 +and CD8+ T cells, augment antigen-presenting function of dendritic cells, enhance cytotoxicity of macrophages and initiate complement cascade activation. VEGF and VEGFR are expressed in immune cells, which are involved in the immunosuppression and cross-talk among immune cells. This review summarizes the expression and function of VEGF-A and VEGF-C in the kidney. The current immunoregulation mechanisms of VEGF signaling pathway inhibitors are reviewed. Finally, combinate strategies are summarized to highlight the proposal for VEGF signaling pathway inhibitors.Copyright © 2023. Published by Elsevier Inc.