肿瘤相关成纤维细胞在肺癌免疫抑制中的研究进展

Research progress of tumor-associated fibroblast in immunosuppression of lung cancer

肺癌是世界范围内首位恶性肿瘤死亡原因,也是目前肿瘤防治中面临最严重的挑战。肺癌肿瘤微环境(TME)中完全的免疫抑制状态是肺癌发生和快速发展的重要原因。肿瘤相关成纤维细胞(CAFs)是一种在肿瘤发生发展初期被异常激活的胞外基质细胞。TME中免疫相关炎症因子是介导CAFs激活的重要因素,激活后的CAFs可以通过减弱抑肿瘤反应、促进免疫抑制细胞募集活化、重塑TME的胞外基质等来加快TME中完全免疫抑制状态的形成。临床上多种耗竭成纤维细胞的新型制剂在肺癌患者的治疗中收效甚微,主要是因为TME功能的可塑性决定了调整CAFs的功能状态比单纯消除更有效。

Lung cancer is the world′s first cause of death from malignant tumors,and it is also the most serious challenge facing cancer prevention and treatment.Complete immunosuppression in the tumor microenvironment(TME)of lung cancer is an important reason for the occurrence and rapid development of lung cancer.Tumor-associated fibroblasts(CAFs)are extracellular stromal cells that are abnormally activated in the early stages of tumorigenesis and development.Immune-related inflammatory factors in TME are important factors that mediate the activation of CAFs.The activated CAFs can accelerate the complete immunosuppressive state of TME by weakening the tumor suppressor response,promoting the recruitment and activation of immunosuppressive cells,and remodeling the extracellular matrix of TME.Clinically,a variety of new preparations that deplete fibroblasts have little effect in the treatment of lung cancer patients,mainly because the plasticity of TME function determines more effective to adjust the functional state of CAFs than simply elimination.