ArticleCancer immunology, immunotherapy : CII2023
Inhibition of the CCR6-CCL20 axis prevents regulatory T cell recruitment and sensitizes head and neck squamous cell carcinoma to radiation therapy.
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 38 papers, 1 of them a synthesis that pooled it.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- A meta-validated immune infiltration-related gene model predicts prognosis and immunotherapy sensitivity in HNSCC.BMC cancer · 2023Pooled it
- Colitis-associated colorectal carcinogenesis: molecular mechanisms and therapeutic potential.Molecular biomedicine · 2026Review
- Radiotherapy-Associated Pain in Head and Neck Cancer: From Clinical Burden to Neuroimmune Modulator.Journal of clinical medicine · 2026Review
- CCL20-CCR6 axis in autoimmune disease and cancer progression: clinical and therapeutic implications.Cell communication and signaling : CCS · 2026Review
- Combining radiotherapy with CAR-T cell therapy for solid tumors: Challenges, mechanisms, and future directions.Precision radiation oncology · 2026Review
- Integrative Multi-Omics and Pan-Cancer Analyses Identify CCL20 as a Prognostic Biomarker with Therapeutic Relevance in Esophageal Cancer.Biomedicines · 2026Article
- From Development to Aging: Dynamic Roles of the Thymic Medulla in T Cell Biology.Immunological reviews · 2026Review
- Radiation-induced remodeling of the T cell landscape in head and neck cancer.Cancer immunology, immunotherapy : CII · 2026Review
- Inhaled Angiopoietin-Like 4 Antisense Oligonucleotide Therapy for Lung Injury and Fibrosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- A preliminary single-cell map of endometriosis suggests roles for fibroblast metabolism and macrophage polarization in disease progression.Functional & integrative genomics · 2026Article
- Boron neutron capture therapy combined with immunotherapy: insights from radiotherapy, BNCT-specific evidence, and future directions.Frontiers in immunology · 2026Review
- Integrating multi-omics and machine learning to uncover CCL20 as a potential regulator of the immunosuppressive microenvironment in lung adenocarcinoma.Frontiers in immunology · 2026Article
- Dynamic integration of CXCL8 or CCL20 signaling with IL-15 or IL-32α reprograms human T-cell functional plasticity.Frontiers in immunology · 2026Article
- The role ofFEMS microbes · 2026Review
- Targeting the chemokine-Treg axes in tumor immune evasion: from mechanisms to therapeutic opportunities.Frontiers in immunology · 2026Review
- Cationic nanoparticles with disrupting neutrophil extracellular traps inhibit the progression of head and neck squamous cell carcinoma.Frontiers in cell and developmental biology · 2026Article
- AI-based pathomics model predicts regulatory T cell infiltration and radiotherapy response in IDH-wild-type glioblastoma.Frontiers in immunology · 2026Article
- Review
- Defining enteric bacterial pathogenesis using organoids:Gut microbes · 2025Article
- Photon and particle radiotherapy induce redundant modular chemotaxis of human lymphocytes.JCI insight · 2025Article
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Authors and funding
17 authors at 1 institution in 1 country.
Funding
Abstract
backgroundRadioresistance of HNSCCs remains a major challenge for effective tumor control. Combined radiotherapy (RT) and immunotherapy (IT) treatment improved survival for a subset of patients with inflamed tumors or tumors susceptible to RT-induced inflammation. To overcome radioresistance and improve treatment outcomes, an understanding of factors that suppress anti-tumor immunity is necessary. In this regard, regulatory T cells (Tregs) are critical mediators of immune suppression in HNSCCs. In this study, we investigated how radiation modulates Treg infiltration in tumors through the chemokine CCL20. We hypothesized that radiation induces CCL20 secretion resulting in Treg infiltration and suppression of anti-tumor immunity.
methodsHuman and mouse HNSCC cell lines with different immune phenotypes were irradiated at doses of 2 or 10 Gy. Conditioned media, RNA and protein were collected for assessment of CCL20. qPCR was used to determine CCL20 gene expression. In vivo, MOC2 cells were implanted into the buccal cavity of mice and the effect of neutralizing CCL20 antibody was determined alone and in combination with RT. Blood samples were collected before and after RT for analysis of CCL20. Tumor samples were analyzed by flow cytometry to determine immune infiltrates, including CD8 T cells and Tregs. Mass-spectrometry was performed to analyze proteomic changes in the tumor microenvironment after anti-CCL20 treatment.
resultsCal27 and MOC2 HNSCCs had a gene signature associated with Treg infiltration, whereas SCC9 and MOC1 tumors displayed a gene signature associated with an inflamed TME. In vitro, tumor irradiation at 10 Gy significantly induced CCL20 in Cal27 and MOC2 cells relative to control. The increase in CCL20 was associated with increased Treg migration. Neutralization of CCL20 reversed radiation-induced migration of Treg cells in vitro and decreased intratumoral Tregs in vivo. Furthermore, inhibition of CCL20 resulted in a significant decrease in tumor growth compared to control in MOC2 tumors. This effect was further enhanced after combination with RT compared to either treatment alone.
conclusionOur results suggest that radiation promotes CCL20 secretion by tumor cells which is responsible for the attraction of Tregs. Inhibition of the CCR6-CCL20 axis prevents infiltration of Tregs in tumors and suppresses tumor growth resulting in improved response to radiation.
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