ArticleCancer immunology, immunotherapy : CII2023
Overcoming cancer-associated fibroblast-induced immunosuppression by anti-interleukin-6 receptor antibody.
Article in Cancer immunology, immunotherapy : CII, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 22 citations in OpenAlex.
- The Cancer Cell Metabolic Reprogramming Remodels the Tumor Microenvironment: Molecular Mechanisms and Therapeutic Strategies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Review
- Cytokines and cancer-associated fibroblasts.Journal of hematology & oncology · 2026Review
- Organ-Specific Migration License (OSML) theory: a novel paradigm for spatiotemporal regulation and intervention of cross-organ immune cell migration in tumor immune responses.Cell communication and signaling : CCS · 2026Review
- RBX1Cancers · 2026Article
- Dynamic feedback between IL-6 and TWIST1 drives pancreatic cancer progression.Translational gastroenterology and hepatology · 2026Article
- L-cystine alleviates necrotizing enterocolitis by regulating ferroptosis and Th17 cell differentiation via the IL-6/STAT3 pathway.Communications biology · 2025Article
- Cellular characteristics of the immune microenvironment of colorectal cancer and progress in immunotherapy research.Annals of medicine · 2025Review
- Tumor microenvironment-mediated immune evasion and resistance in prostate cancer: mechanisms, cross-talk, and therapeutic opportunities.Clinical and experimental medicine · 2025Review
- Intrapleural dual blockade of IL-6 and PD-L1 reprograms CAF dynamics and the tumor microenvironment in lung cancer-associated malignant pleural effusion.Respiratory research · 2025Article
- Novel treatment strategy targeting interleukin-6 induced by cancer associated fibroblasts for peritoneal metastasis of gastric cancer.Scientific reports · 2025Article
- Metabolic Reprogramming Shapes the Progression and Therapeutic Landscape of Ovarian Cancer.Cancer management and research · 2025Review
- Single-cell RNA-Seq reveals the heterogeneity of fibroblasts within the tympanojugular paraganglioma microenvironment.Heliyon · 2024Article
- LAG-3 : recent developments in combinational therapies in cancer.Cancer science · 2024Review
- Interleukin-6 serves as a critical factor in various cancer progression and therapy.Medical oncology (Northwood, London, England) · 2024Review
- Fibroblast activation protein-targeted near-infrared photoimmunotherapy depletes immunosuppressive cancer-associated fibroblasts and remodels local tumor immunity.British journal of cancer · 2024Article
- The cancer-associated fibroblasts interact with malignant T cells in mycosis fungoides and promote the disease progression.Frontiers in immunology · 2024Article
- CPT1C-positive cancer-associated fibroblast facilitates immunosuppression through promoting IL-6-induced M2-like phenotype of macrophage.Oncoimmunology · 2024Article
- Immunomodulatory Effect of Hypericin-Mediated Photodynamic Therapy on Oral Cancer Cells.Pharmaceutics · 2023Article
- Article
Corrections and comments
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Authors and funding
18 authors at 1 institution in 1 country.
Funding
Abstract
Cancer-associated fibroblasts (CAFs) are a critical component of the tumor microenvironment and play a central role in tumor progression. Previously, we reported that CAFs might induce tumor immunosuppression via interleukin-6 (IL-6) and promote tumor progression by blocking local IL-6 in the tumor microenvironment with neutralizing antibody. Here, we explore whether an anti-IL-6 receptor antibody could be used as systemic therapy to treat cancer, and further investigate the mechanisms by which IL-6 induces tumor immunosuppression. In clinical samples, IL-6 expression was significantly correlated with α-smooth muscle actin expression, and high IL-6 cases showed tumor immunosuppression. Multivariate analysis showed that IL-6 expression was an independent prognostic factor. In vitro, IL-6 contributed to cell proliferation and differentiation into CAFs. Moreover, IL-6 increased hypoxia-inducible factor 1α (HIF1α) expression and induced tumor immunosuppression by enhancing glucose uptake by cancer cells and competing for glucose with immune cells. MR16-1, a rodent analog of anti-IL-6 receptor antibody, overcame CAF-induced immunosuppression and suppressed tumor progression in immunocompetent murine cancer models by regulating HIF1α activation in vivo. The anti-IL-6 receptor antibody could be systemically employed to overcome tumor immunosuppression and improve patient survival with various cancers. Furthermore, the tumor immunosuppression was suggested to be induced by IL-6 via HIF1α activation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.