title: 14-3-3ζ regulates immune response through Stat3 signaling in oral squamous cell carcinoma.
abstract: Ectopic expression of 14-3-3ζ has been found in various malignancies, including lung cancer, liver cancer, head and neck squamous cell carcinoma (HNSCC), and so on. However, the effect of 14-3-3ζ in the regulation of interactions between tumor cells and the immune system has not been previously reported. In this study, we aimed to investigate whether and how 14-3-3ζ is implicated in tumor inflammation modulation and immune recognition evasion. In oral squamous cell carcinoma (OSCC) cell lines and cancer tissues, we found that 14-3-3ζ is overexpressed. In OSCC cells, 14-3-3ζ knockdown resulted in the up-regulated expression of inflammatory cytokines. In contrast, 14-3-3ζ introduction attenuated cytokine expression in human normal keratinocytes and fibroblasts stimulated with interferon-γ (IFN-γ) and lipopolysaccharide (LPS). Furthermore, supernatants from 14-3-3ζ knockdown OSCC cells dramatically altered the response of peritoneal macrophages, dendritic cells and tumor-specific T cells. Interestingly, Stat3 was found to directly interact with 14-3-3ζ and its disruption relieved the inhibition induced by 14-3-3ζ in tumor inflammation. Taken together, our studies provide evidence that 14-3-3ζ may regulate tumor inflammation and immune response through Stat3 signaling in OSCC.
authors.affiliation: Department of Oral and Maxillofacial Surgery, the First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Xinguang
authors.initials: X
authors.lastname: Han
authors.affiliation: Department of Oral and Maxillofacial Surgery, the First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Yongfu
authors.initials: Y
authors.lastname: Han
authors.affiliation: Department of Oral and Maxillofacial Surgery, the First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Huifeng
authors.initials: H
authors.lastname: Jiao
authors.affiliation: School of Stomatology Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Yaqiong
authors.initials: Y
authors.lastname: Jie
mesh_terms: D048948:14-3-3 Proteins / Q000235:genetics* / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D009062:Mouth Neoplasms / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D048948:14-3-3 Proteins; D016207:Cytokines; D008070:Lipopolysaccharides; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C572235:YWHAZ protein, human; D007371:Interferon-gamma
keywords: 14-3-3ζ; Stat3; immune response; oral squamous cell carcinoma; tumor inflammation