肿瘤相关成纤维细胞与成纤维细胞活化蛋白在肿瘤免疫治疗中的研究进展

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-associatedfibroblasts，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 activationprotein，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。它由肿瘤问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。

Advance of tumor-associated fibroblasts and fibroblast activation protein in tumor immunity

Tumor progression is a multistep process which depends not only on accumulation of mutations in cancer cells but also on the interactions between cancer cells and their microenvironment. Fibroblasts in the tumor- stromal compartment named tumor associated fibroblasts may suppress the immune response, impair the antitumor immune response and ultimately hinder the immunotherapy. Fibreblast activation protein（FAP） is a surface antigen especially expressed on TAFs, it is an integral membrane serine peptidase, a member of the group of II integral serine proteases, stromal tumor associated fibroblasts expressing fibroblast activation protein are the first identified stromal cells, which activated via the association between stromal fibroblasts and cancer cells. In contrast to tumor cells, which are genetically unstable and mutate frequently, the presence of gene- tically more stable fibroblasts in the turnor-stromal compartment makes them an optimal target for cancer immunotherapy. This paper is targeted TAF and FAP in tumor immunotherapy in the application were introduced in this paper, based on the tumor stromal microenvironment immune therapy provide reference.