The role of Foxp3 and Tbet co-expressing Treg cells in lung carcinoma
The role of Foxp3 and Tbet co-expressing Treg cells in lung carcinoma
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DOI：
10.1080/2162402x.2018.1456612
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发表时间：
2018-01-01
期刊：
影响因子：
7.2
通讯作者：
Finotto, Susetta
中科院分区：
文献类型：
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作者：
Kachler, Katerina;Holzinger, Corinna;Finotto, Susetta
尽管Tbet和Foxp 3在免疫系统以及肿瘤生物学中具有相反的作用，但最近的研究表明存在表达Tbet和Foxp 3的CD 4（+）T细胞。虽然Tbet（+）Foxp 3（+）T细胞目前是一个深入研究的主题，但对它们的生物学功能，特别是在癌症中的生物学功能知之甚少。在这里，我们发现荷瘤小鼠肺部的Tbet（+）Foxp 3（+）CD 4（+）T细胞大量积聚，由免疫抑制细胞因子TGF β介导。这与先前的研究一致，证明了TGF β在癌症免疫发病机制中的重要作用。通过收集小鼠模型和人类疾病中的结果，我们证明，产生IFN γ的抗肿瘤T-bet+ Th 1 CD 4 + T细胞转化为免疫抑制性Tbet和Foxp 3-PD 1共表达调节细胞可能代表TGF β介导的抗肿瘤免疫阻断的另一个重要机制。
Despite the opposite roles of Tbet and Foxp3 in the immune system as well as in tumour biology, recent studies have demonstrated the presence of of CD4(+) T cells, expressing both, Tbet and Foxp3. Although Tbet(+)Foxp3(+) T cells are currently a subject of intense research, less is known about their biological function especially in cancer. Here we found a considerable accumulation of Tbet(+)Foxp3(+)CD4(+) T cells, mediated by the immunosuppressive cytokine TGF beta in the lungs of tumour bearing mice. This is in line with previous studies, demonstrating the important role of TGF beta for the immunopathogenesis of cancer. By gathering results both in murine model and in human disease, we demonstrate that, the conversion of IFN gamma producing anti-tumoral T-bet+Th1 CD4+ T cells into immunosuppressive Tbet and Foxp3-PD1 co-expressing regulatory cells could represent an additional important mechanism of TGF beta-mediated blockade of anti-tumour immunity.