Immune signature-based risk stratification and prediction of immune checkpoint inhibitor's efficacy for lung adenocarcinoma

Cancer Immunol Immunother. 2021 Jun;70(6):1705-1719. doi: 10.1007/s00262-020-02817-z. Epub 2021 Jan 2.

Abstract

Background: Lung adenocarcinoma (LUAD) is a common pulmonary malignant disease with a poor prognosis. There were limited studies investigating the influences of the tumor immune microenvironment on LUAD patients' survival and response to immune checkpoint inhibitors (ICIs).

Methods: Based on TCGA-LUAD dataset, we constructed a prognostic immune signature and validated its predictive capability in the internal as well as total datasets. Then, we explored the differences of tumor-infiltrating lymphocytes, tumor mutation burden, and patients' response to ICI treatment between the high-risk score group and low-risk score group.

Results: This immune signature consisted of 17 immune-related genes, which was an independent prognostic factor for LUAD patients. In the low-risk score group, patients had better overall survival. Although the differences were non-significant, patients with low-risk scores had more tumor-infiltrating follicular helper T cells and fewer macrophages (M0), which were closely related to clinical outcomes. Additionally, the total TMB was markedly decreased in the low-risk score group. Using immunophenoscore as a surrogate of ICI response, we found that patients with low-risk scores had significantly higher immunophenoscore.

Conclusion: The 17-immune-related genes signature may have prognostic and predictive relevance with ICI therapy but needs prospective validation.

Keywords: Immune checkpoint inhibitor; Immunotherapy; Lung adenocarcinoma; Prognostic model; The tumor immune microenvironment; Tumor mutation burden.

MeSH terms

  • Adenocarcinoma of Lung / drug therapy
  • Adenocarcinoma of Lung / genetics
  • Adenocarcinoma of Lung / immunology
  • Adenocarcinoma of Lung / pathology*
  • Biomarkers, Tumor / genetics*
  • Humans
  • Immune Checkpoint Inhibitors / therapeutic use*
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics
  • Lung Neoplasms / immunology
  • Lung Neoplasms / pathology*
  • Lymphocytes, Tumor-Infiltrating / pathology*
  • Macrophages / pathology*
  • Mutation*
  • Prognosis
  • Survival Rate

Substances

  • Biomarkers, Tumor
  • Immune Checkpoint Inhibitors