ArticleBMC cancer2021
Downregulation of CCL22 and mutated NOTCH1 in tongue and mouth floor squamous cell carcinoma results in decreased Th2 cell recruitment and expression, predicting poor clinical outcome.
Article in BMC cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
6 citing papers in PubMed, 1 synthesis or guideline pooled it, 9 citations in OpenAlex.
- The prognostic value of lymphatic vessel density in squamous cell carcinoma of the tongue: a systematic review and meta-analysis.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2026Pooled it
- The CCL17/CCL22-CCR4 Axis in Pain Pathogenesis: A Comprehensive Review of Immune-Mediated Mechanisms and Therapeutic Opportunities.Molecular neurobiology · 2025Review
- Downstream STING pathways IRF3 and NF-κB differentially regulate CCL22 in response to cytosolic dsDNA.Cancer gene therapy · 2024Article
- 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
- An Immune-Related Gene Signature Can Predict Clinical Outcomes and Immunotherapeutic Response in Oral Squamous Cell Carcinoma.Frontiers in genetics · 2022Article
- Comprehensive analyses identify RIPOR2 as a genomic instability-associated immune prognostic biomarker in cervical cancer.Frontiers in immunology · 2022Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveTongue and mouth floor squamous cell carcinoma (T/MF SCC) exhibits a high rate of local recurrence and cervical lymph node metastasis. The effect of the tumor microenvironment on T/MF SCC remains unclear. MATERIALS AND
methodsTranscriptome and somatic mutation data of patients with T/MF SCC were obtained from HNSC projects of the Cancer Genome Atlas. Immune infiltration quantification in early- (clinical stage I-II) and advanced-stage (clinical stage III-IV) T/MF SCC was performed using single sample Gene Set Enrichment Analysis and MCPcounter. Differentially expressed gene data were filtered, and their function was assessed through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Kaplan-Meier survival curve analysis and Cox regression model were conducted to evaluate the survival of patients with the CCL22 signature. Maftools was used to present the overview of somatic mutations.
resultsIn T/MF SCC, T helper (Th)2 cell counts were significantly increased in patients with early-stage disease compared to those with advanced-stage disease. Expression of the Th2 cell-related chemokine, CCL22, was downregulated in patients with advanced-stage T/MF SCC. Univariate and multivariate Cox analyses revealed that CCL22 was a good prognostic factor in T/MF SCC. A nomogram based on the expression of CCL22 was constructed to serve as a prognostic indicator for T/MF SCC. NOTCH1 mutations were found at a higher rate in patients with advanced-stage T/MF SCC than in those with early-stage T/MF SCC, resulting in the inhibition of the activation of the NOTCH1-Th2 cell differentiation pathway. The expression levels of CCL22, GATA-3, and IL4 were higher in patients with early-stage T/MF SCC than in those with advanced-stage T/MF SCC.
conclusionIn T/MF SCC, high expression of CCL22 may promote the recruitment of Th2 cells and help predict a better survival. Mutations in NOTCH1 inhibit the differentiation of Th2 cells, facilitating tumor progression through a decrease in Th2 cell recruitment and differentiation.
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