Intrinsically altered lung‐resident γδT cells control lung melanoma by producing interleukin‐17A in the elderly

Autor: Zhigang Tian, Yin Chen, Guodong Shen, Gan Shen, Tingjuan Xu, Weiping Xu, Dake Huang, Shilian Hu, Yongyan Chen, Wen Chen, Min Cheng
Rok vydání: 2020
Předmět:
Zdroj: Aging Cell
ISSN: 1474-9726
1474-9718
Popis: 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.
In the aged mice (20–24 months), the number of lung‐resident γδT cells was significantly increased with altered gene expression compared with the young mice (10–16 weeks). Aged lung γδT cells predominantly produced interleukin‐17A (IL‐17A), which played a critical role in resistance to the development of lung melanoma in the aged. Furthermore, the anti‐tumor activity of aged lung γδT17 cells was not affected by alterations in the load and composition of commensal microbiota.
Databáze: OpenAIRE
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