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1、调节性T细胞（Treg）介导的免疫逃逸在肿瘤中的作用调节性 T 细胞（regulatory T cells, Treg）是一群具有免疫抑制功能的 T 细胞，主要包括天然型 Treg（CD4+CD25+Treg）和诱导型 Treg（iTreg）两大类。Treg 在慢性免疫应答中可以限制自身免疫造成的组织损伤，但却给肿瘤逃避机体的免疫创造了条件。Treg 能够通过以下多种途径抑制机体免疫反应，促使肿瘤细胞发生免疫耐受逃逸：（1）Treg 通过分泌多种抑制性细胞因子，如TGF-、IL-10、IL-35等，发挥免疫抑制效应1；（2）Treg 表面组成性表达 CD25（IL2R链），能与效应 T 细胞竞
2、争性结合并大量消耗IL-2，从而抑制效应细胞（如 CD4+和 CD8+T 淋巴细胞）的增殖2；（3）Treg表面组成性表达CTLA-4，能与树突细胞（DC）表面配体CD80和CD86相互作用，从而阻断它们的共刺激功能和随后的T细胞活化和功能3；（4）在肿瘤微环境中 Treg 可以表达颗粒酶 B，以颗粒酶 B/穿孔素依赖的方式使 NK、CTL 等细胞溶解，抑制机体抗肿瘤免疫4。iTreg 细胞由多种成分在外周诱导产生，主要以细胞因子依赖(IL-10 和 TGF-)发挥免疫负调节作用。CD4+CD25+Treg特异性表达转录因子FOXP3，FOXP3在 Treg 的分化发育及其介导的肿瘤免疫逃逸中
3、发挥关键作用，因而是鉴别肿瘤微环境中Treg的有效靶标5。越来越多的研究表明Treg 介导的免疫监视逃逸在肿瘤的发生发展过程中发挥着重要作用6, 7。Treg已被发现在肿瘤患者外周血和肿瘤组织中过量增加，包括乳腺癌8、肠癌9、胃癌10、白血病11、黑色素瘤12、非小细胞肺癌13、卵巢癌14和肝癌15。大多数证据表明肿瘤微环境中Treg高表达和预后不良有关。然而，Treg浸润到肿瘤内部和周围却没有显著作用，甚至是对患者有益的，这可能和肿瘤类型，Treg分布和定位有关。如Fridman 等研究发现，结直肠癌患者肿瘤组织浸润高密度的 FOXP3+Treg 细胞提示患者的预后较好16。尽管如此，目前人
4、们普遍认为Treg 浸润的肿瘤抑制免疫干预的疗效，因而成为肿瘤免疫治疗的新方向。如抗CTLA-4单抗，在II期临床试验中能有效延长IV期黑色素瘤患者的存活时间。能够阻断体外CCL22-介导的Treg和Th2招募过程的小分子趋化因子受体拮抗剂或单抗也已进入I期临床试验阶段17。最近一些研究为Treg的免疫抑制功能提供了新的机制。Vizio等发现FoxP3+Treg细胞参与Th17启动的癌变过程18。Treg抑制宫颈癌肿瘤微环境中存在的肿瘤浸润Th1和Th2效应分子19。此外，FOXP3 +调节性T细胞包括不同亚群，其中CXCR3+ Treg细胞，已被证明特异性地控制体内的I型T细胞反应。Redj
5、imi等发现CXCR3+ Treg细胞高度富集于人类卵巢癌，特别是在实体肿瘤中，控制I型T细胞应答，导致免疫抑制20。综上，关于 Treg 细胞与肿瘤的关系以及作用机制有待深入研究，为肿瘤的免疫治疗提供更多新的思路，从而为肿瘤的治疗带来新的突破。参考文献1.Kanamori M, Nakatsukasa H, Okada M, Lu Q, Yoshimura A. Induced Regulatory T Cells: Their Development, Stability, and Applications. Trends in immunology 2016.2.Sakaguchi S,
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