Ex Vivo Interferon Gamma Production by Peripheral Immune Cells Predicts Survival in Lung Adenocarcinoma

Clin Lung Cancer. 2019 May;20(3):e299-e308. doi: 10.1016/j.cllc.2019.01.002. Epub 2019 Jan 26.

Abstract

Background: Lung cancer is one of the most lethal malignancies, with a 5-year survival rate < 20% in patients with stage IV lung cancer. Impaired host immunity is associated with lung cancer pathogenesis, and interferon gamma (IFN-γ) plays an important role in antitumor immune surveillance. We evaluated the clinical significance of ex vivo production of IFN-γ in patients with lung adenocarcinoma.

Patients and methods: We reviewed the medical records of 109 treatment-naive patients with lung adenocarcinoma who had undergone IFN-γ releasing assay. Differences in the IFN-γ level in nil and mitogen tubes were defined as ex vivo IFN-γ production. Correlation analysis was performed to evaluate the correlation between ex vivo IFN-γ production, cancer staging, and Eastern Cooperative Oncology Group performance status. The optimal cutoff values of low and high ex vivo IFN-γ production were estimated using receiver operator characteristic curve analysis. Cox proportional hazard analyses were used to evaluate the prognostic factors of 1-year overall patient survival.

Results: Ex vivo IFN-γ production correlated with N stage, M stage, cancer staging, and Eastern Cooperative Oncology Group performance status. Low ex vivo IFN-γ production (ex vivo IFN-γ production ≤ 7.79 IU/mL) was independently associated with 1-year overall survival (odds ratio = 3.289; 95% confidence interval, 1.573-6.872; P = .002). Additionally, low ex vivo IFN-γ production was an independent predictor of 1-year overall survival in patients with stage IV cancer (odds ratio = 3.156; 95% confidence interval, 1.473-6.760; P = .003).

Conclusion: Ex vivo IFN-γ production before treatment might be a useful biomarker for predicting prognosis in patients with lung adenocarcinoma.

Keywords: Biomarker; IFN-γ; IFN-γ releasing assay; Lung cancer; Prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma of Lung / diagnosis*
  • Adenocarcinoma of Lung / immunology
  • Adenocarcinoma of Lung / mortality
  • Aged
  • Biomarkers
  • Cells, Cultured
  • Female
  • Humans
  • Interferon-gamma / metabolism*
  • Killer Cells, Natural / immunology*
  • Lung Neoplasms / diagnosis*
  • Lung Neoplasms / immunology
  • Lung Neoplasms / mortality
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Survival Analysis
  • T-Lymphocytes / immunology*

Substances

  • Biomarkers
  • Interferon-gamma