Heterogeneity of Treg/Th17 According to Cancer Progression and Modification in Biliary Tract Cancers via Self-Producing Cytokines.
Dig Dis Sci
; 65(10): 2937-2948, 2020 10.
Article
em En
| MEDLINE
| ID: mdl-31853779
ABSTRACT
BACKGROUND/AIM:
We previously demonstrated that inflammatory cytokine interleukin-6 (IL-6) was produced during cancer progression, worked together with transforming growth factor-beta 1 (TGF-ß1), and induced the epithelial-mesenchymal transition (EMT) with chemo-resistance against gemcitabine (GR) at the invasion front of biliary tract cancers (BTCs). However, the significance of cytokine-induced T cell accumulation at the tumor microenvironment in biliary tract cancer (BTC) is not well understood. Because these cytokines (IL-6 and TGF-ß1) are able to differentiate naïve T cells into Foxp3-expressing T cells (Tregs) and/or IL-17-producing T helper 17 (Th17) cells, we investigated the relationship between heterogeneous, cancer-producing cytokines and T cell differentiation.METHODS:
In total, 127 curative resected specimens from patients with BTCs at Osaka University Hospital between 2000 and 2012 were evaluated for IL-6, TGF-ß1, Tregs, and Th17 cells by immunohistochemistry. The ability of BTC-GR cells to undergo T cell differentiation was investigated in vitro.RESULTS:
Tregs accumulated at the tumor center and Th17 cells accumulated at the invasion front during cancer progression and/or metastasis; each signaled poor prognosis. Treg accumulation was related to TGF-ß1 expression by cancer cells, and Th17 cell accumulation was related to IL-6 expression by cancer cells, in resected specimens; this was confirmed in vitro. Compared with parent cells, GR cells produced IL-6 but not TGF-ß1 in a time-dependent manner, had EMT features, and induced T cell differentiation to Th17 cells but not Tregs.CONCLUSION:
Cytokines produced by cancer cells (IL-6 and TGF-ß1) induced heterogeneity of Tregs and Th17 cells in the tumor microenvironment, supporting progression of BTC.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias do Sistema Biliar
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Diferenciação Celular
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Citocinas
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Linfócitos do Interstício Tumoral
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Linfócitos T Reguladores
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Células Th17
Tipo de estudo:
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Dig Dis Sci
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Japão