Abstract
Purpose
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.
Methods
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.
Results
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).
Conclusion
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.
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Availability of data and material
All data generated or analyzed during this study are available from the corresponding author on reasonable request.
Code availability
Graphpad 6.0 software.
Abbreviations
- Blk:
-
B lymphoid kinase
- CCR6:
-
C–C motif chemokine receptor 6
- GTEx:
-
Genotype-tissue expression
- IFN:
-
Interferon
- IL:
-
Interleukin
- LTBR:
-
Lymphotoxin-β receptor
- LUAD:
-
Lung adenocarcinoma
- LUSC:
-
Squamous cell carcinoma
- NK:
-
Natural killer
- NSCLC:
-
Non-small cell lung cancer
- OS:
-
Overall survival
- TCGA:
-
The cancer genome atlas
- TGF:
-
Transforming growth factor
- TME:
-
Tumor microenvironment
- TNF:
-
Tumor necrosis factor
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Funding
This work was supported by Natural Science Foundation of Anhui Province (2008085MH277), and National Natural Science Foundation of China (81471552).
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KC performed the study design, acquisition and analysis of data, and drafted the manuscript. XM participated in the data analysis. MC obtained the funding, conceived the study, and participated in the experimental design, data analysis, and the paper writing.
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Cui, K., Mei, X. & Cheng, M. Increased interleukin-17A-producing γδT cells predict favorable survival in elderly patients with LUAD and LUSC. J Cancer Res Clin Oncol 147, 3289–3298 (2021). https://doi.org/10.1007/s00432-021-03742-z
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DOI: https://doi.org/10.1007/s00432-021-03742-z