PD-L1与TGF-β协同调控肿瘤免疫逃逸:机制与双靶向治疗进展OA
PD-L1 and TGF-β cooperatively regulate tumor immune escape:mechanisms and advances in dual-targeting therapy
程序性死亡配体 1(programmed cell death ligand 1,PD-L1)抑制剂虽在肿瘤治疗中取得突破,但其疗效受限于肿瘤微环境异质性及多重免疫抑制通路.近年来研究发现,转化生长因子 β(transforming growth factor-β,TGF-β)通过代谢重编程、上皮-间质转化及 SOX家族因子等途径,与 PD-L1协同驱动肿瘤细胞免疫逃逸.目前,已有多种 PD-L1/TGF-β双特异性抗体(bispecific antibody,bsAb)在早期临床试验中显示出优良的治疗潜力,但其仍面临毒性及耐药性挑战.本文系统综述了 PD-L1与 TGF-β协同调控肿瘤免疫逃逸的机制,总结了 bsAb的临床研究进展,探讨了新型药物设计及生物标志物开发策略,旨在为肿瘤联合免疫治疗策略的开发提供新思路.
While programmed cell death ligand 1(PD-L1)inhibitors have yielded breakthroughs in tumor therapy,their efficacy is constrained by the heterogeneity of the tumor microenvironment and multiple immunosuppressive pathways.In recent years,research has revealed that transforming growth factor-β(TGF-β)synergistically drives tumor cell immune escape with PD-L1 via pathways such as metabolic reprogramming,epithelial-mesenchymal transition,and SOX family factors.Currently,various PD-L1/TGF-β bispecific antibodies(bsAbs)have exhibited promising therapeutic potential in early-phase clinical trials,yet they still confront challenges related to toxicity and drug resistance.This article systematically reviews the mechanisms by which PD-L1 and TGF-β synergistically regulate tumor immune escape,summarizes the clinical research progress of bsAbs,and discusses strategies for novel drug design and biomarker development,with the aim of offering new insights for the development of combined tumor immunotherapy strategies.
何倩倩;杨艳丽;张晗;陈哲宇;姬菩忠
中国人民解放军联勤保障部队第九四〇医院病理科,兰州 730050||甘肃中医药大学第一临床医学院,兰州 730000中国人民解放军联勤保障部队第九四〇医院病理科,兰州 730050中国人民解放军联勤保障部队第九四〇医院病理科,兰州 730050中国人民解放军联勤保障部队第九四〇医院病理科,兰州 730050||西北民族大学医学院,兰州 730030中国人民解放军联勤保障部队第九四〇医院病理科,兰州 730050
医药卫生
PD-L1TGF-β双特异性抗体代谢重编程上皮-间质转化免疫逃逸
programmed cell death ligand 1transforming growth factor-βbispecific antibodymetabolic reprogrammingepithelial-mesenchymal transitionimmune escape
《中国临床医学》 2026 (3)
533-543,11
甘肃省卫生健康行业科研项目(GSWSKY2024-59),甘肃省科技计划资助项目(22JR5RA022).Supported by Scientific Research Project of Gansu Provincial Health Industry(GSWSKY2024-59)and Gansu Provincial Science and Technology Program Funding Project(22JR5RA022).
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