Intratumor hypoxia promotes immune tolerance by inducing regulatory T cells via TGF-β1 in gastric cancer.
Intratumor hypoxia promotes immune tolerance by inducing regulatory T cells via TGF-β1 in gastric cancer.
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肿瘤内缺氧通过通过TGF-β1在胃癌中诱导调节性T细胞来促进免疫耐受性。
DOI：
10.1371/journal.pone.0063777
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Shen XZ
中科院分区：
文献类型：
--
作者：
Deng B;Zhu JM;Wang Y;Liu TT;Ding YB;Xiao WM;Lu GT;Bo P;Shen XZ
调节性T细胞（Treg）介导的免疫抑制是肿瘤免疫逃避的重要机制之一，也是肿瘤免疫治疗成功的主要障碍。缺氧是实体瘤的常见特征，与增强的免疫抑制、降低的治疗反应、恶性进展和局部侵袭相关。不幸的是，胃癌中缺氧和Treg介导的免疫耐受之间的联系仍然知之甚少。在我们的研究中，发现TcR和缺氧诱导因子-1 α彼此呈正相关，并且随着肿瘤的进展而增加。随后的体外研究表明，低氧条件下胃癌细胞的上清液可通过TGF-β1诱导Foxp 3的表达。这些结果证实了TGF-A作为治疗靶点在胃癌治疗中的重要作用，并为今后胃癌免疫治疗的设计提供了有益的思路。
Regulatory T cell (Treg)-mediated immunosuppression represents one of the crucial tumor immune evasion mechanisms and is a main obstacle for successful tumor immunotherapy. Hypoxia, a common feature of solid tumors, has been associated with potentiated immunosuppression, decreased therapeutic response, malignant progression and local invasion. Unfortunately, the link between hypoxia and Treg-mediated immune tolerance in gastric cancer remains poorly understood. In our study, Tregs and hypoxia inducible factor-1α were found to be positively correlated with each other and were increased with the tumor progression. A subsequent in vitro study indicated that supernatants derived from gastric cancer cells under hypoxic condition, could induce the expression of Foxp3 via TGF-β1. These findings confirmed the crucial role of Tregs as a therapeutic target in gastric cancer therapy and provided helpful thoughts for the design of immunotherapy for gastric cancer in the future.
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影响因子：
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