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除了依赖于肿瘤细胞自身的恶性增殖以外,肿瘤的发生和发展还依赖于肿瘤细胞与肿瘤间质微环境的相互作用。肿瘤间质中存在的肿瘤相关成纤维细胞(tumor-associated fibroblasts,TAF)能够诱导免疫抑制,是肿瘤免疫治疗中的一大障碍。在TAF上存在一种成纤维细胞激活蛋白(fibroblast activation protein,FAP),它在细胞表面发挥作用,是一种膜丝氨酸肽酶,是II型丝氨酸蛋白酶家族成员之一,具有二肽肽酶及胶原酶活性,在肿瘤微环境中表达FAP的肿瘤相关成纤维细胞是最早被鉴定的一种肿瘤间质细胞类型。它由肿瘤间质中的成纤维细胞与癌细胞相互作用而活化,是肿瘤微环境中最主要的宿主细胞,具有促进肿瘤细胞生长、侵袭及免疫抑制的作用,而且基因组稳定不易耐药,有望成为肿瘤免疫治疗的新靶标。就靶向TAF和FAP在肿瘤免疫治疗中的研究做一综述,为基于肿瘤间质微环境的免疫治疗提供参考。
In addition to relying on the malignant proliferation of tumor cells, the occurrence and development of tumors depend on the interaction between tumor cells and the tumor interstitial microenvironment. The existence of tumor-associated fibroblasts (TAFs) in the tumor stroma induces immunosuppression and is a major obstacle in tumor immunotherapy. In TAF, there is a fibroblast activation protein (FAP) that acts on the cell surface and is a membrane serine peptidase, a member of the serine type II serine protease family, with dipeptidyl peptidase and Collagenase activity. Tumor-associated fibroblasts expressing FAP in the tumor microenvironment were the earliest identified types of tumor stromal cells. It is activated by the interaction of fibroblasts and cancer cells in the tumor stroma, which is the most important host cell in the tumor microenvironment, and has the function of promoting tumor cell growth, invasion and immunosuppression. Moreover, the genome is stable and resistant to drug resistance. It is expected that Become a new target for tumor immunotherapy. This review summarizes the research of targeting TAF and FAP in tumor immunotherapy and provides a reference for immunotherapy based on tumor interstitial microenvironment.