Green Jesse A, Arpaia Nicholas, Schizas Michail, Dobrin Anton, Rudensky Alexander Y
Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, NY.
Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY.
J Exp Med. 2017 Dec 4;214(12):3565-3575. doi: 10.1084/jem.20170356. Epub 2017 Oct 16.
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.
效应T细胞和调节性T（Treg）细胞分别在促进和对抗实体器官癌变过程中发挥作用，这被视为机体对肿瘤或自身抗原耐受的破坏与建立之间的动态平衡。我们认为肿瘤相关T细胞可能通过非淋巴器官中的T细胞用于在损伤或应激时维持自身的独特机制来促进恶性肿瘤的发展。最近的研究表明，Treg细胞能够以与其免疫抑制能力无关的方式参与组织修复。利用小鼠肺肿瘤移植模型，我们发现表皮生长因子家族成员双调蛋白在肿瘤内Treg细胞中显著上调。此外，T细胞特异性双调蛋白缺陷导致肺肿瘤进展明显延迟。观察到的肿瘤进展抑制与T细胞免疫反应性或Treg细胞和效应T细胞数量的可检测变化无关。这些观察结果表明，肿瘤内Treg细胞和效应T细胞通过产生通常参与组织修复和维持的因子促进肿瘤生长，这是一种新的“非免疫”模式。
