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（T reg）细胞分别参与对立和促进实体器官癌变的参与，被视为突破与建立对肿瘤或自身抗原的耐受性之间的转移平衡。我们认为，肿瘤相关性T细胞可能通过非淋巴器官中T细胞所使用的独特机制促进恶性肿瘤，以协助其在受伤或应激时得以维持。最近的研究表明，T reg细胞可以以与其免疫抑制能力不同的方式参与组织修复。使用小鼠肺部肿瘤的可移植模型，我们发现表皮生长因子家族成员双调蛋白在肿瘤内T reg细胞中显着上调。此外，T细胞限制的双调蛋白缺乏导致肺肿瘤进展明显延迟。在肿瘤进展中观察到的这种威慑与可检测到的T细胞免疫应答或T reg和效应T细胞数量的变化无关。这些观察结果表明，肿瘤内T reg和效应T细胞通过产生通常参与组织修复和维持的因子来促进肿瘤生长的一种新颖的“非免疫”方式。