ArticleDigestive diseases and sciences2020
Heterogeneity of Treg/Th17 According to Cancer Progression and Modification in Biliary Tract Cancers via Self-Producing Cytokines.
Article in Digestive diseases and sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 23 citations in OpenAlex.
- Tertiary lymphoid structure topotypes in intrahepatic cholangiocarcinoma: spatial immunity, checkpoint-response associations, and therapeutic reprogramming.Frontiers in immunology · 2026Review
- Stratifying cholangiocarcinoma: tumor microenvironment, molecular drivers, and novel immunotherapeutic approaches.Clinical and molecular hepatology · 2026Review
- Spatially resolved whole-transcriptomic profiling of EGFR-mutated lung adenocarcinomas stratified by PD-L1 expression.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- N-glycosylated LTβR increases the Th17/Treg cell ratio in liver cancer by blocking RORC ubiquitination and FOXP3 transcription.Cell death & disease · 2025Article
- Identification of PANoptosis-relevant subgroups and predicting signature to evaluate the prognosis and immune landscape of patients with biliary tract cancer.Hepatology international · 2024Article
- Review
- Focusing on the Immune Cells: Recent Advances in Immunotherapy for Biliary Tract Cancer.Cancer management and research · 2024Review
- SPARC accelerates biliary tract cancer progression through CTGF-mediated tumor-stroma interactions: SPARC as a prognostic marker of survival after neoadjuvant therapy.Journal of cancer research and clinical oncology · 2023Article
- Immunobiology of cholangiocarcinoma.Journal of hepatology · 2023Review
- Impact of pathological complete response following neoadjuvant chemotherapy (gemcitabine, nab-paclitaxel, S-1) and radiation for borderline resectable pancreatic cancer: a case report and review of literature.Surgical case reports · 2022Article
- MiR-192-5p/RB1/NF-κBp65 signaling axis promotes IL-10 secretion during gastric cancer EMT to induce Treg cell differentiation in the tumour microenvironment.Clinical and translational medicine · 2022Article
- ACAT-1-Regulated Cholesteryl Ester Accumulation Modulates Gemcitabine Resistance in Biliary Tract Cancer.Annals of surgical oncology · 2022Article
- Tumor Microenvironment and its Implications for Antitumor Immunity in Cholangiocarcinoma: Future Perspectives for Novel Therapies.International journal of biological sciences · 2022Review
- Curcuminoids as Modulators of EMT in Invasive Cancers: A Review of Molecular Targets With the Contribution of Malignant Mesothelioma Studies.Frontiers in pharmacology · 2022Review
- Interleukin-17 activates JAK2/STAT3, PI3K/Akt and nuclear factor-κB signaling pathway to promote the tumorigenesis of cervical cancer.Experimental and therapeutic medicine · 2021Article
- Recent advances in the role of Th17/Treg cells in tumor immunity and tumor therapy.Immunologic research · 2021Review
- Review
- A Comparison of Automated Perfusion- and Manual Diffusion-Based Human Regulatory T Cell Expansion and Functionality Using a Soluble Activator Complex.Cell transplantationArticle
Corrections and comments
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Authors and funding
19 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND/
aimWe previously demonstrated that inflammatory cytokine interleukin-6 (IL-6) was produced during cancer progression, worked together with transforming growth factor-beta 1 (TGF-β1), 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-β1) 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.
methodsIn total, 127 curative resected specimens from patients with BTCs at Osaka University Hospital between 2000 and 2012 were evaluated for IL-6, TGF-β1, Tregs, and Th17 cells by immunohistochemistry. The ability of BTC-GR cells to undergo T cell differentiation was investigated in vitro.
resultsTregs 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-β1 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-β1 in a time-dependent manner, had EMT features, and induced T cell differentiation to Th17 cells but not Tregs.
conclusionCytokines produced by cancer cells (IL-6 and TGF-β1) induced heterogeneity of Tregs and Th17 cells in the tumor microenvironment, supporting progression of BTC.
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