国自然调节性T细胞Treg介导的免疫逃逸在肿瘤中的作用

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，主要分为天然型Treg （CD4+CD25+Treg和诱导型Treg （ iTreg ）两大类。Treg在慢性免疫应答屮可以限制自身免疫造成的组织损伤，但却也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-3、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 a链），能与效应T细胞竞争

2、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）的增殖蔦（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（ 4）在肿瘤微环境屮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*0 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- 3 ）发挥免疫负调节作用。CD4+CD25+Treg特异性表达转录因子F0XP3 F0XP3在Treg的分化发育及其介导的肿瘤免疫逃逸屮发挥关键作用，因

3、而是鉴别肿瘤微环境屮Treg的有效靶标5o预防性FoxP3 DNA/重组蛋白疫苗（Foxp3疫苗）在无肿瘤条件下促进针对Treg的免疫性，通过靶向Treg和MDS （来促进针对肿瘤的免疫应答，这可以被用作潜在的免疫治疗方法笃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“。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、肠癌“、胃癌“、白血病入黑色素瘤仁非小细胞肺癌人卵巢癌和肝癌大多数证据表明肿瘤微环境中Tteg高表达和预后不良有关。然而Fridman等研究发现，结直 肠癌患者肿瘤组织浸润 高密度的F0XP3+Treg细胞提示患者的预后较好仃

4、，这可能是和肿瘤类型、Treg的分布和定位有关。尽管如此，目前人们普遍认为活的Treg细胞抑制抗肿瘤免疫因而它成为了肿瘤免疫治疗的新方向。女口，有研究发现后萎缩性增生（ PAH在CD4 + Tregs存在下直接进入前列腺 癌的可能途径，并且表明即使在原发性肿瘤建立之前，抗肿瘤免疫应答的转化也可能开始 叩 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 临床试验阶段呛在肾细胞癌屮，由新的肽拮抗剂肽-R29引发的CXCR4拮抗作用能有效地逆 转Teff增 殖的Treg抑制，

5、这可能是肿瘤免疫应答的可靠生物标志物最近一些研究为Treg的免疫抑制功能提供了新的机制。Vizio等发现FoxP3+Treg细胞22参与Thl7启动的癌变过程 。Treg抑制宫颈癌肿瘤微环境中存在的肿瘤浸润 Thl和Th2效 应分子讯此外，F0XP3 +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。Redjimi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S HIV感染诱导CD8 +CD28-CD1271oCD39 + Treg细胞的显着扩增，其频率与临床疾病和慢性免疫细胞活化的

6、迹彖 相关花 综上，关于Treg细胞与肿瘤的关系以及作用机制还有待深入的研究，以此为肿瘤的免疫治疗提供更多新的思路，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, andTrends in immunology 2016Applications.2. Sakaguchi S, Miyara M, Costantino CM, Hafler DA. F0XP3+ regulatory

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