1. 延安大学基础医学院,陕西 延安 716000;2. 空军军医大学实验动物中心,西安 710032)
1. Medical College of Yan’an University, Yan’an 716000, China; 2. Laboratory Animal Center, the Air Force Medical University, Xi’an 710032, China
胰腺导管癌(pancreatic ductal adenocarcinoma,PDAC)是一种常见的胰腺癌,其发病隐匿、发展迅速、恶性程度高。传统的治疗方法对其效果不佳,这与PDAC具有丰富的细胞外基质(extracellular matrix,ECM)密不可分,而癌症相关成纤维细胞(cancer-associated fibroblast,CAF)是ECM中最重要的组成部分。CAF可通过分泌大量效应分子,与肿瘤免疫微环境(tumor microenvironment,TME)内的其他免疫成分相互作用,从而形成免疫抑制性TME,使癌细胞能够逃避免疫系统的监视,进而促进肿瘤生长、侵袭、转移、ECM重塑甚至产生耐药性。本文就靶向CAF在PDAC免疫治疗中的应用研究进展进行综述,重点阐述了通过消耗CAF、抑制CAF分泌效应分子、重编程CAF、限制CAF诱导的ECM重塑等方式,促使TME由免疫抑制状态转变为免疫激活状态的研究策略,期望产生更加有效的治疗效果,从而为PDAC的免疫治疗提供新策略。
Pancreatic ductal adenocarcinoma (PDAC) is a common type of pancreatic cancer that is insidious, develops rapidly, and is highly malignant. Traditional treatment strategies are ineffective for PDAC because of its rich extracellular matrix (ECM). Cancer-associated fibroblast (CAF) are the most important component of the ECM, and interact with other immune components in the tumor microenvironment (TME) by secreting numerous effector molecules to form an immunosuppressive TME, which may then allow cancer cells to evade immune system surveillance, promote tumor growth, invasion, and metastasis, and induce ECM remodeling and drug resistance. This review summarizes research progress on the application of targeted CAF in PDAC immunotherapy. We focus on exploring research strategies that promote the transition of TME from an immunosuppressive to an immune-activated state through depleting CAF, inhibiting effector molecules secreted by CAF, reprogramming CAF, and limiting CAF-induced ECM remodeling. This review aims to support the production of more effective therapeutic strategies and provide new method for the immunotherapy of PDAC.
刘星宇,秦靖,胡耀华,郭梦甜,赵菊梅,师长宏.靶向CAF策略在PDAC免疫治疗中的应用研究进展[J].中国实验动物学报,2024,32(11):1472~1481.
复制
