IL-17 Affects the Progression, Metastasis, and Recurrence of Laryngeal Cancer via the Inhibition of Apoptosis through Activation of the PI3K/AKT/FAS/FASL Pathways

J Immunol Res. 2020 Dec 18:2020:2953191. doi: 10.1155/2020/2953191. eCollection 2020.

Abstract

Background: Cytokines play important roles in the development and prognosis of laryngeal cancer (LC). Interleukin-17 (IL-17) from a distinct subset of CD4+ T cells may significantly induce cancer-elicited inflammation to prevent tumor immune surveillance.

Methods: The expression levels of IL-17 were examined among 60 patients with LC. Immunofluorescence colocalization experiments were performed to verify the localization of IL-17 and FAS/FASL in Hep-2 and Tu212 cells. The role of IL-17 was determined using siRNA techniques in the LC cell line.

Results: In the LC patients, cytokines were dysregulated in LC tissues compared with normal tissues. It was found that IL-17 was overexpressed in a cohort of 60 LC tumors paired with nontumor tissues. Moreover, high IL-17 expression was significantly associated with the advanced T category, the late clinical stage, differentiation, lymph node metastasis, and recurrence. In addition, the time course expression of FAS and FASL was observed after stimulation and treatment with the IL-17 stimulator. Finally, in vitro experiments demonstrated that IL-17 functioned as an oncogene by inhibiting the apoptosis of LC cells via the PI3K/AKT/FAS/FASL pathways.

Conclusions: In summary, these findings demonstrated for the first time the role of IL-17 as a tumor promoter and a prometastatic factor in LC and indicated that IL-17 may have an oncogenic role and serve as a potential prognostic biomarker and therapeutic target in LC.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Apoptosis / genetics
  • Apoptosis / immunology
  • Cell Line, Tumor
  • Cytokines / metabolism
  • Disease Progression
  • Fas Ligand Protein / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunomodulation / genetics
  • Interleukin-17 / genetics*
  • Interleukin-17 / metabolism
  • Laryngeal Neoplasms / genetics*
  • Laryngeal Neoplasms / metabolism*
  • Laryngeal Neoplasms / pathology
  • Lymphocyte Activation / genetics
  • Lymphocyte Activation / immunology
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • ROC Curve
  • Signal Transduction
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Young Adult
  • fas Receptor / metabolism*

Substances

  • Cytokines
  • Fas Ligand Protein
  • Interleukin-17
  • fas Receptor
  • Proto-Oncogene Proteins c-akt