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

Sung Soo Ahn, Minkyung Kwon, Mindong Sung, Seung Min Jung, Sang Won Lee, Yong Beom Park, Sang Taek Kim, Jason Jungsik Song

Research output: Contribution to journalArticle

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. 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.

Original languageEnglish (US)
Pages (from-to)e299-e308
JournalClinical Lung Cancer
Volume20
Issue number3
DOIs
StatePublished - May 2019

Fingerprint

Interferon-gamma
Cell Survival
Lung Neoplasms
Neoplasm Staging
Biomarkers
Adenocarcinoma of lung
Survival
Odds Ratio
Confidence Intervals
Neoplasms
Mitogens
Non-Small Cell Lung Carcinoma
Immunotherapy
Medical Records
Immunity
Survival Rate
Cytokines

Keywords

  • Biomarker
  • IFN-γ
  • IFN-γ releasing assay
  • Lung cancer
  • Prognosis

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

Cite this

Ahn, S. S., Kwon, M., Sung, M., Jung, S. M., Lee, S. W., Park, Y. B., ... Song, J. J. (2019). Ex Vivo Interferon Gamma Production by Peripheral Immune Cells Predicts Survival in Lung Adenocarcinoma. Clinical Lung Cancer, 20(3), e299-e308. https://doi.org/10.1016/j.cllc.2019.01.002

Ex Vivo Interferon Gamma Production by Peripheral Immune Cells Predicts Survival in Lung Adenocarcinoma. / Ahn, Sung Soo; Kwon, Minkyung; Sung, Mindong; Jung, Seung Min; Lee, Sang Won; Park, Yong Beom; Kim, Sang Taek; Song, Jason Jungsik.

In: Clinical Lung Cancer, Vol. 20, No. 3, 05.2019, p. e299-e308.

Research output: Contribution to journalArticle

Ahn, Sung Soo ; Kwon, Minkyung ; Sung, Mindong ; Jung, Seung Min ; Lee, Sang Won ; Park, Yong Beom ; Kim, Sang Taek ; Song, Jason Jungsik. / Ex Vivo Interferon Gamma Production by Peripheral Immune Cells Predicts Survival in Lung Adenocarcinoma. In: Clinical Lung Cancer. 2019 ; Vol. 20, No. 3. pp. e299-e308.
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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. 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.",
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N2 - 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.

AB - 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.

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