The Levels of Interferon-gamma Release as a Biomarker for Non-small-cell Lung Cancer Patients Receiving Immune Checkpoint Inhibitors

Anticancer Res. 2019 Nov;39(11):6231-6240. doi: 10.21873/anticanres.13832.

Abstract

Background/aim: The present study aimed to prospectively examine the usefulness of interferon-gamma (IFN-γ) release (IGR) as a biomarker in non-small-cell lung cancer patients receiving immune checkpoint inhibitor treatment (ICI-Tx).

Patients and methods: IGR was measured using enzyme-linked immunosorbent assay at four time points: within 14 days before ICI-Tx (T1), and 8±3 (T2), 22±7 (T3), and 43±7 (T4) days after ICI-Tx.

Results: Twenty-nine patients were divided into three groups based on IFN-γ levels in the IGR-positive control: Group-1 (n=8) with <10 IU/ml at T1, Group-2 (n=12) with a decrease in IFN-γ levels to <10 IU/ml at T3 and/or T4, and Group-3 (n=9) without changes in IFN-γ levels. Early progression and ICI-induced interstitial pneumonitis were frequently observed in Group-1 and Group-2, respectively. Group-3 exhibited more treatment cycles than the other groups. All three groups showed clear differences in clinical outcomes.

Conclusion: IFN-γ levels could be a biomarker for ICI-Tx.

Keywords: Non-small-cell lung cancer; biomarker; immune checkpoint inhibitors; immune-related adverse events; interferon-gamma release assay; interstitial pneumonitis.

Publication types

  • Observational Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antineoplastic Agents, Immunological / adverse effects
  • Antineoplastic Agents, Immunological / therapeutic use*
  • B7-H1 Antigen / antagonists & inhibitors
  • B7-H1 Antigen / metabolism
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Disease Progression
  • Female
  • Humans
  • Immunotherapy / adverse effects
  • Immunotherapy / methods
  • Interferon-gamma / blood
  • Interferon-gamma / metabolism*
  • Latent Tuberculosis / diagnosis
  • Latent Tuberculosis / etiology
  • Latent Tuberculosis / metabolism
  • Lung Diseases, Interstitial / etiology
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / therapy
  • Male
  • Middle Aged
  • Nivolumab / therapeutic use
  • Prospective Studies
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*
  • Time Factors

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents, Immunological
  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human
  • Nivolumab
  • atezolizumab
  • Interferon-gamma
  • pembrolizumab