ArticleCancers2021
Cancer-Associated Fibroblast-Derived IL-6 Determines Unfavorable Prognosis in Cholangiocarcinoma by Affecting Autophagy-Associated Chemoresponse.
Article in Cancers, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 54 citations in OpenAlex.
- Review
- Longitudinal analysis of peripheral blood immune status and prognosis dynamic prediction for advanced colon cancer with first-line chemotherapy.Cancer immunology, immunotherapy : CII · 2026Article
- Cancer-Associated fibroblasts regulate the development of cholangiocarcinoma through IL-6/STAT3/AKR1C3 signaling axis.Scientific reports · 2026Article
- Integrative Sequencing and Proteogenomic Approaches to Intratumoral Heterogeneity in Cholangiocarcinoma: Implications for Precision Diagnosis and Therapy.Medical sciences (Basel, Switzerland) · 2026Review
- Harnessing cellular immunotherapy for cholangiocarcinoma: an integrated roadmap for overcoming resistance.Frontiers in immunology · 2026Review
- Stratifying cholangiocarcinoma: tumor microenvironment, molecular drivers, and novel immunotherapeutic approaches.Clinical and molecular hepatology · 2026Review
- Cancer-associated fibroblasts, clinicopathological characteristics and prognosis of liver cancer: A systematic review and meta-analysis based on real-world research.World journal of gastrointestinal oncology · 2025Article
- SARS-CoV2 and Anti-COVID-19 mRNA Vaccines: Is There a Plausible Mechanistic Link with Cancer?Cancers · 2025Review
- Article
- Immunotherapy in biliary tract cancer: reshaping the tumour microenvironment and advancing precision combination strategies.Frontiers in immunology · 2025Review
- Single-cell analysis defines LGALS1+ fibroblasts that promote proliferation and migration of intrahepatic cholangiocarcinoma.Journal of molecular cell biology · 2024Article
- Crosstalk between cancer-associated fibroblasts and regulated cell death in tumors: insights into apoptosis, autophagy, ferroptosis, and pyroptosis.Cell death discovery · 2024Review
- Resveratrol Promotes Self-digestion to Put Cancer to Sleep.Journal of cancer prevention · 2024Article
- Article
- Immunohistochemical Profile of p62/SQSTM1/Sequestosome-1 in Human Low- and High-Grade Intracranial Meningiomas.Analytical cellular pathology (Amsterdam) · 2024Article
- Evaluation of selected circulating cytokines from the IL-6 family - interleukin 6, oncostatin M, and cardiotrophin-1 - in gastro-entero-pancreatic and bronchial neuroendocrine tumours.Contemporary oncology (Poznan, Poland) · 2024Article
- Identification of the function ofTranslational cancer research · 2023Article
- The Prognosis of Cancer Depends on the Interplay of Autophagy, Apoptosis, and Anoikis within the Tumor Microenvironment.Cell biochemistry and biophysics · 2023Review
- Automated Analysis for the Prevalence of Cancer-Associated Fibroblasts in Resected Specimens of Intrahepatic Cholangiocarcinoma is a Simple and Reliable Evaluation System.Annals of surgical oncology · 2023Article
- Active Autophagy Is Associated with Favorable Outcome in Patients with Surgically Resected Cholangiocarcinoma.Cancers · 2023Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundInterleukin-6 (IL-6) released by cancer-associated fibroblasts (CAFs) has been shown to associate with the malignant behavior of cholangiocarcinoma (CCA). Here, we aimed to validate with clinical and molecular data the hypothesis that CAF infiltration and release of IL-6 predict poor prognosis in CCA patients following dysregulation of autophagy in cancer cells.
methodsStromal IL-6 and cancer-cell-associated autophagy proteins LC3 and p62 were assayed by Tissue MicroArray immunohistochemistry and their expression correlated with overall survival (OS) in a cohort of 70 CCA patients. The 5-FU cytotoxicity and autophagy were determined in CCA cells cultured with CAF-conditioned medium.
resultsWe show that patients bearing a CCA with low production of stromal IL-6 and active autophagy flux in the cancer cells have the best prognosis and this correlates with a more effective response to post-operative chemotherapy. A similar trend was observed in CCA patients from the TCGA database. In vitro genetic manipulation of IL-6 production by primary CAFs isolated from human CCA showed that IL-6 impairs the autophagy-associated apoptotic response to 5-FU in human CCA cells. Stromal IL-6 inhibition of autophagy in cancer cells was confirmed in an animal model of CCA.
conclusionOur data support a therapeutic strategy that includes autophagy-enhancing drugs along with adjuvants limiting the stromal inflammation (i.e., the secretion of IL-6) to improve the survival of CCA patients.
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