Roles of naïve CD4+ T cells and their differentiated subtypes in lung adenocarcinoma and underlying potential regulatory pathways.
J Transl Med
; 22(1): 781, 2024 Aug 22.
Article
em En
| MEDLINE
| ID: mdl-39175022
ABSTRACT
BACKGROUND:
Naïve CD4+ T cells and their differentiated counterparts play a significant regulatory role in the tumor immune microenvironment, yet their effects on lung adenocarcinoma (LUAD) are not fully understood.METHODS:
We utilized Mendelian randomization to assess the causal association between naïve CD4+ T cells and LUAD. Employing a modified single-sample Gene Set Enrichment Analysis (ssGSEA) algorithm with The Cancer Genome Atlas (TCGA) database, we determined the infiltration levels of naïve CD4+ T cells and their differentiation subtypes and investigated their correlation with clinical characteristics. Potential regulatory pathways of T helper cells were identified through Mantel tests and Kyoto Encyclopedia of Genes and Genomes (KEGG) database enrichment analysis.RESULTS:
Mendelian randomization analysis revealed an inhibitory effect of naïve CD4+ T cells on LUAD (false discovery rate < 0.05), which was corroborated by observational experiments using TCGA database. Specifically, T helper cell type 2 demonstrated a promotive effect on LUAD in terms of overall, disease-free, and progression-free survival (p < 0.05). Moreover, regulatory T cells exhibited a protective effect on LUAD in terms of disease-specific survival (p < 0.01). Concurrently, we explored the overall impact of naïve CD4+ T cell differentiation subtypes on LUAD, revealing upregulation in pathways such as neutrophil degranulation, MAPK family signaling pathways, and platelet activation, signaling, and aggregation.CONCLUSION:
Naïve CD4+ T cells and their differentiated counterparts play essential regulatory roles in the tumor immune microenvironment, demonstrating bidirectionality in their effects.Thus, elucidating the mechanisms and developing novel cell differentiation-inducing agents will benefit anti-cancer therapy.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T CD4-Positivos
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Diferenciação Celular
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Adenocarcinoma de Pulmão
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Neoplasias Pulmonares
Limite:
Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Transl Med
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China