A nonimmune function of T cells in promoting lung tumor progression.
A nonimmune function of T cells in promoting lung tumor progression.
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DOI：
10.1084/jem.20170356
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发表时间：
2017-12-04
期刊：
影响因子：
--
通讯作者：
Rudensky AY
中科院分区：
文献类型：
--
作者：
Green JA;Arpaia N;Schizas M;Dobrin A;Rudensky AY
格林等人。发现 T 细胞衍生的双调蛋白似乎独立于免疫反应而促进肺肿瘤进展，这表明 T 细胞可以通过产生通常与组织修复相关的因子来促进肿瘤生长。效应 T 细胞和调节性 T (T reg) 细胞分别参与对抗和促进实体器官癌变，被视为破坏肿瘤或自身抗原耐受性与建立耐受性之间的平衡变化。我们认为，肿瘤相关 T 细胞可能通过非淋巴器官中 T 细胞使用的不同机制促进恶性肿瘤，以协助其在受伤或应激时维持。最近的研究表明，T reg 细胞可以以与其免疫抑制能力分离的方式参与组织修复。使用小鼠肺肿瘤移植模型，我们发现双调蛋白（表皮生长因子家族的成员）在肿瘤内 T reg 细胞中显着上调。此外，T细胞限制性双调蛋白缺乏导致肺肿瘤进展明显延迟。这种观察到的肿瘤进展抑制作用与 T 细胞免疫反应性或 T reg 和效应 T 细胞数量的可检测变化无关。这些观察结果表明肿瘤内 T reg 和效应 T 细胞有一种新的“非免疫”模式，通过产生通常参与组织修复和维护的因子来促进肿瘤生长。
Green et al. find that T cell–derived amphiregulin facilitates lung tumor progression seemingly independently of the immune response, suggesting that T cells can promote tumor growth through the production of factors normally associated with tissue repair. The involvement of effector T cells and regulatory T (T reg) cells in opposing and promoting solid organ carcinogenesis, respectively, is viewed as a shifting balance between a breach versus establishment of tolerance to tumor or self-antigens. We considered that tumor-associated T cells might promote malignancy via distinct mechanisms used by T cells in nonlymphoid organs to assist in their maintenance upon injury or stress. Recent studies suggest that T reg cells can participate in tissue repair in a manner separable from their immunosuppressive capacity. Using transplantable models of lung tumors in mice, we found that amphiregulin, a member of the epidermal growth factor family, was prominently up-regulated in intratumoral T reg cells. Furthermore, T cell–restricted amphiregulin deficiency resulted in markedly delayed lung tumor progression. This observed deterrence in tumor progression was not associated with detectable changes in T cell immune responsiveness or T reg and effector T cell numbers. These observations suggest a novel “nonimmune” modality for intratumoral T reg and effector T cells in promoting tumor growth through the production of factors normally involved in tissue repair and maintenance.
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