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

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. Immunotherapies targeting the immune checkpoint receptor have shown promising results in non–small-cell lung cancer. Nevertheless, there are limitations in current biomarkers for evaluating the function of immune cells. Interferon gamma (IFN-γ) is a proinflammatory cytokine that contributes to cancer recognition and elimination. This study demonstrated ex vivo IFN-γ production might be a biomarker for predicting patient prognosis in lung adenocarcinoma.