Cancer is an age‐associated disease, potentially related to the altered immune system of elderly individuals. However, cancer has gradually decreased incidence in the eldest globally such as the most common lung cancer, the mechanisms of which remain to be elucidated. In this study, it was found that the number of lung‐resident γδT cells was significantly increased with altered gene expression in aged mice (20–24 months) versus young mice (10–16 weeks). Aged lung Vγ4⁺ and Vγ6⁺ γδT cells predominantly produced interleukin‐17A (IL‐17A), resulting in increased levels in the serum and lungs. Moreover, the aged mice exhibited smaller tumors and reduced numbers of tumor foci in the lungs after challenge with intravenous injection of B16/F10 melanoma cells compared with the young mice. Aged lung Vγ4⁺ and Vγ6⁺ γδT cells were highly cytotoxic to B16/F10 melanoma cells with higher expression levels of CD103. The markedly longer survival of the challenged aged mice was dependent on γδT17 cells, since neutralization of IL‐17A or depletion of indicated γδT cells significantly shortened the survival time. Consistently, supplementation of IL‐17A significantly enhanced the survival time of young mice with lung melanoma. Furthermore, the anti‐tumor activity of aged lung γδT17 cells was not affected by alterations in the load and composition of commensal microbiota, as demonstrated through co‐housing of the aged and young mice. Intrinsically altered lung γδT17 cells underlying age‐dependent changes control lung melanoma, which will help to better understand the lung cancer progression in the elderly and the potential use of γδT17 cells in anti‐tumor immunotherapy.

中文翻译：

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内在改变的肺驻留γδT细胞通过产生老年人白细胞介素17A来控制肺部黑色素瘤。

癌症是一种与年龄有关的疾病，可能与老年人的免疫系统改变有关。然而，癌症已逐渐降低了全球范围内最老的发病率，例如最常见的肺癌，其机制尚待阐明。在这项研究中，发现年龄较大的小鼠（20-24个月）相对于年轻小鼠（10-16周）的基因表达改变后，肺驻留γδT细胞的数量显着增加。老年肺Vγ4 ⁺和Vγ6 ⁺γδT细胞主要产生白介素17A（IL-17A），导致血清和肺中的水平升高。此外，与年轻小鼠相比，经静脉内注射B16 / F10黑色素瘤细胞攻击后，老年小鼠表现出较小的肿瘤并减少了肺中的肿瘤灶数量。老年肺Vγ4 ⁺和Vγ6 ⁺γδT细胞对具有较高CD103表达水平的B16 / F10黑色素瘤细胞具有高度细胞毒性。受攻击的衰老小鼠的明显更长的存活期取决于γδT17细胞，因为中和IL-17A或清除指定的γδT细胞会大大缩短存活时间。始终如一地，补充IL-17A可以显着延长幼年肺黑色素瘤小鼠的生存时间。此外，老年小鼠和青年小鼠的共居证明，老年肺γδT17细胞的抗肿瘤活性不受共生菌群负荷和组成变化的影响。年龄依赖性变化背后的内在改变的肺γδT17细胞控制着肺黑色素瘤，