APE1 facilitates PD-L1-mediated progression of laryngeal and hypopharyngeal squamous cell carcinoma

Int Immunopharmacol. 2021 Aug:97:107675. doi: 10.1016/j.intimp.2021.107675. Epub 2021 May 6.

Abstract

Laryngeal squamous cell carcinoma (LSCC) and hypopharyngeal squamous cell carcinoma (HSCC) seriously affect the life quality of patients. Nowadays, immunotherapy is widely used in the treatment of cancer. Tumor-infiltrating lymphocytes (TILs), programmed cell death 1 (PD-1) and its ligand programmed cell death ligand 1 (PD-L1) play key roles in the immunotherapy of cancer. Moreover, study has reported that the upregulation of PD-L1 and apurinic/apyrimidinic endonuclase 1 (APE1) are associated with tumorigenesis and poor prognosis of gastric cancer. In the present study, the number of CD3+ T lymphocytes and the expressions of PD-1 and PD-L1 in LSCC and HSCC were detected in clinical samples. In addition, the expressions of PD-L1 and APE1 and their correlation were explored. The results showed that PD-1+ T lymphocytes were wildly infiltrated and PD-L1 was overexpressed in LSCC and HSCC tissues. PD-1 had a positive correlation with cancer progression, and glottic and subglottic LSCC tissues might have a more active immune microenvironment. Moreover, the results showed that upregulated co-expression of PD-L1 and APE1 was a biomarker of LSCC, and APE1 could regulate the expression of PD-L1 through NF-κB signaling pathway. In conclusion, the combine detection of the expressions of PD-1, PD-L1 and APE1 will provide predictive value for the treatment of LSCC and HSCC via immune checkpoint inhibitors, which will help us to identify the patient population more likely to benefit from the immune checkpoint inhibitors based on the tumor immune microenvironment.

Keywords: APE1; Hypopharyngeal squamous cell carcinoma; Laryngeal squamous cell carcinoma; PD-1; PD-L1; TILs.

Publication types

  • Observational Study

MeSH terms

  • B7-H1 Antigen / antagonists & inhibitors
  • B7-H1 Antigen / genetics*
  • B7-H1 Antigen / metabolism
  • Biomarkers, Tumor / antagonists & inhibitors
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Cell Line, Tumor
  • Chemotherapy, Adjuvant / methods
  • DNA-(Apurinic or Apyrimidinic Site) Lyase / metabolism*
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Expression Regulation, Neoplastic / immunology
  • Humans
  • Hypopharyngeal Neoplasms / diagnosis
  • Hypopharyngeal Neoplasms / genetics
  • Hypopharyngeal Neoplasms / immunology*
  • Hypopharyngeal Neoplasms / therapy
  • Immune Checkpoint Inhibitors / pharmacology
  • Immune Checkpoint Inhibitors / therapeutic use
  • Kaplan-Meier Estimate
  • Laryngeal Neoplasms / diagnosis
  • Laryngeal Neoplasms / genetics
  • Laryngeal Neoplasms / immunology*
  • Laryngeal Neoplasms / therapy
  • Male
  • Middle Aged
  • NF-kappa B / metabolism
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Programmed Cell Death 1 Receptor / metabolism
  • Signal Transduction / genetics
  • Signal Transduction / immunology
  • Squamous Cell Carcinoma of Head and Neck / diagnosis
  • Squamous Cell Carcinoma of Head and Neck / genetics
  • Squamous Cell Carcinoma of Head and Neck / immunology*
  • Squamous Cell Carcinoma of Head and Neck / therapy
  • Tumor Microenvironment / drug effects
  • Tumor Microenvironment / genetics
  • Tumor Microenvironment / immunology
  • Up-Regulation / drug effects
  • Up-Regulation / immunology

Substances

  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human
  • Immune Checkpoint Inhibitors
  • NF-kappa B
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • APEX1 protein, human
  • DNA-(Apurinic or Apyrimidinic Site) Lyase