ArticleCancer science2019
Cancer-associated fibroblast-derived interleukin-1β activates protumor C-C motif chemokine ligand 22 signaling in head and neck cancer.
Article in Cancer science, 2019. 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, 63 citations in OpenAlex.
- Cancer-associated fibroblasts as a target in head and neck squamous cell carcinoma: bridging mechanisms to therapy with drugs, adjuvants, and nanotechnology.Discover oncology · 2026Review
- Cytokines and cancer-associated fibroblasts.Journal of hematology & oncology · 2026Review
- Targeting the chemokine-Treg axes in tumor immune evasion: from mechanisms to therapeutic opportunities.Frontiers in immunology · 2026Review
- Article
- Unlocking the crucial role of cancer-associated fibroblasts in tumor metastasis: Mechanisms and therapeutic prospects.Journal of advanced research · 2025Review
- Ferroptotic Neutrophils Induce Immunosuppression and Chemoresistance in Breast Cancer.Cancer research · 2025Article
- Fibroblast-immune crosstalk in oral squamous cell carcinoma: from tumor promotion to immune evasion.Frontiers in immunology · 2025Review
- The role of transcription factors in the crosstalk between cancer-associated fibroblasts and tumor cells.Journal of advanced research · 2025Review
- Identification of key immune cells infiltrated in lung adenocarcinoma microenvironment and their related long noncoding RNA.iScience · 2024Article
- Downstream STING pathways IRF3 and NF-κB differentially regulate CCL22 in response to cytosolic dsDNA.Cancer gene therapy · 2024Article
- Activation of the CCL22/CCR4 causing EMT process remodeling under EZH2-mediated epigenetic regulation in cervical carcinoma.Journal of Cancer · 2024Article
- Spatial subsetting enables integrative modeling of oral squamous cell carcinoma multiplex imaging data.iScience · 2023Article
- Cancer-associated fibroblasts: tumor defenders in radiation therapy.Cell death & disease · 2023Review
- Increase of the T-reg-recruiting chemokine CCL22 expression in a progressive course of cervical dysplasia.Journal of cancer research and clinical oncology · 2023Article
- Small molecule metabolites: discovery of biomarkers and therapeutic targets.Signal transduction and targeted therapy · 2023Review
- Review
- Identification and Biological Validation of a Chemokine/Chemokine Receptor-Based Risk Model for Predicting Immunotherapeutic Response and Prognosis in Head and Neck Squamous Cell Carcinoma.International journal of molecular sciences · 2023Article
- Signaling pathways in cancer-associated fibroblasts: recent advances and future perspectives.Cancer communications (London, England) · 2023Review
- The Role of Immune Modulatory Cytokines in the Tumor Microenvironments of Head and Neck Squamous Cell Carcinomas.Cancers · 2022Review
- [Research Status of Tumor-associated Fibroblasts Regulating Immune Cells].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2022Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
Oral cancer, a subtype of head and neck cancer, is characterized by increased infiltrating regulatory T cells (Treg); however, the pathological significance of the increase in Tregs in disease prognosis and progression and their underlying mechanism remain unestablished. C-C motif chemokine ligand 22 (CCL22) has been implicated in the recruitment of Tregs. We used RT-qPCR to determine CCL22 mRNA expression in clinical specimens and cultured cells. Loss-of-function and gain-of-function studies were carried out to analyze the effects of CCL22 modulations on cell proliferation, migration, invasion, and tumorigenesis and the mechanism involved in the deregulation of CCL22. In oral cancer specimens, CCL22 mRNA was upregulated. The increase was not only associated with reduced disease-free survival but also strongly correlated with an increase in FOXP3 mRNA, a master regulator of Treg development and functions. Silencing CCL22 expression reduced cell proliferation, migration, and invasion, whereas ectopic overexpression showed opposite effects. Manipulation of CCL22 expression in cancer cells altered tumorigenesis in both immune-compromised and -competent mice, supporting both autonomous and non-autonomous actions of CCL22. Release of interleukin 1β (IL-1β) from cancer-associated fibroblasts (CAF) induces CCL22 mRNA expression in oral cancer cells by activating transcription factor nuclear factor kappa B (NF-κB). Our data support a model in which CAF-derived IL-1β, CCL22, and its receptor CCR4 foster a protumor environment by promoting cell transformation and Treg infiltration. Intervention of the IL-1β-CCL22-CCR4 signaling axis may offer a novel therapeutic strategy for oral cancer treatment.
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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.