Increased interleukin-17A-producing γδT cells predict favorable survival in elderly patients with LUAD and LUSC

Aging is closely related to the occurrence of many diseases, including cancer, and involves changes in the immune microenvironment. γδT cells are important components of resident lymphocytes in mucosal tissues. However, little is known about the effects that the aged lung has on γδT cells and their prognostic significance in non-small cell lung cancer.

In the current study, the expression of γδTCR and IL-17A was measured by immunohistochemistry in paraffin-embedded lung tissues from 168 patients with adenocarcinoma (LUAD) and 144 patients with squamous cell carcinoma (LUSC). Furthermore, gene transcription patterns in LUAD and LUSC tumors and normal controls were extracted from TCGA and GTEx databases and were analyzed.

High frequency of γδT cells was observed in patients with LUAD and LUSC, whereas the levels of CD4 + T cells, CD8 + T cells and CD56 + cells were decreased. Elevated γδT cells in tumors were mainly IL-17A-releasing γδT17 cells, which were found to be enriched in aged patients. High γδT cell levels positively corelated with the overall survival (OS) of patients, especially the 5-year OS in the elderly. Further analysis of gene transcription patterns indicated that increased expression of LTBR, HES1, RORC, CCR6, IL1, and IL23A may contribute to the transformation of the tumor microenvironment in a manner conducive to γδT17 cell development and differentiation. Finally, gene analysis between different age groups revealed that the expression of CCR6 and IL7 in LUAD, as well as Hes1, IL7, and IL23A in LUSC, were remarkably higher in elderly (age ≥ 60 years) than in younger individuals (age < 60 years).

Our findings suggest that intrinsic alterations in the aging lung lead to γδT17 cell enrichment, which subsequently may exert anti-tumor effects in the elderly.