Differential expression of programmed death-1 and its ligand, programmed death ligand-1 in oral squamous cell carcinoma with and without oral submucous fibrosis

Arch Oral Biol. 2020 Nov:119:104916. doi: 10.1016/j.archoralbio.2020.104916. Epub 2020 Sep 17.

Abstract

Objective: The aim of our study was to investigate the expression of programmed death ligand-1 (PD-L1)/programmed death-1 (PD-1) between oral squamous cell carcinoma (OSCC) patients with and without oral submucous fibrosis (OSF), and its correlation with clinic-pathologic features and its prognostic value.

Methods: PD-L1 and PD-1 expression was evaluated by immunohistochemical staining, double immunofluorescent staining and real-time PCR, and the correlation of PD-L1/PD-1 expression with clinical outcome was assessed.

Results: The level of PD-L1 expression was significantly higher in OSCC with OSF than in OSCC without OSF (p = 0.006). Moreover, PD-L1 expression was strongly correlated with lymph node metastasis (p = 0.016), and advanced tumor stage (p = 0.030). Increased PD-L1 expression was positively correlated with the incidence of OSCC with OSF (p = 0.006, p = 0.008, respectively). PD-L1 expression was an independent marker of unfavorable prognosis (p = 0.035, p = 0.048, respectively). High PD-L1 expression had a significantly worse outcome in OSCC patients with OSF (p = 0.014). Double immunofluorescent staining showed that OSCC with OSF were more strongly expressed both PD-L1 and PD-1 than OSCC without OSF. Moreover, the expression of PD-L1 were upregulated in OSCC tissues than normal control (p = 0.0422), and both PD-L1 and PD-1 was significantly higher in OSCC with OSF than OSCC without OSF tissues (p = 0.0043 and, p = 0.0012, respectively).

Conclusions: The present study suggested that PD-L1 may be an unfavorable indicator for prognosis. PD-L1/PD-1 signaling might play an important role in the malignant transformation of OSF, and targeting PD-L1/PD-1 signaling may be a new therapeutic strategy for OSCC, especially in OSCC patients with OSF.

Keywords: Oral squamous cell carcinoma; Oral submucous fibrosis; Prognosis; Programmed death 1; Programmed death ligand-1.

MeSH terms

  • B7-H1 Antigen / metabolism*
  • Carcinoma, Squamous Cell / complications
  • Carcinoma, Squamous Cell / metabolism*
  • Humans
  • Ligands
  • Mouth Neoplasms / complications
  • Mouth Neoplasms / metabolism*
  • Oral Submucous Fibrosis / complications
  • Oral Submucous Fibrosis / metabolism*
  • Prognosis
  • Programmed Cell Death 1 Receptor / metabolism*

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • Ligands
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor