ITGB2 as a prognostic indicator and a predictive marker for immunotherapy in gliomas

Cancer Immunol Immunother. 2022 Mar;71(3):645-660. doi: 10.1007/s00262-021-03022-2. Epub 2021 Jul 27.

Abstract

Purpose: Glioma is the most common primary tumor in the brain, accounting for 81% of intracranial malignancies. Nowadays, cancer immunotherapy has become a novel and revolutionary treatment for patients with advanced, highly aggressive tumors. However, to date, there are no effective biomarkers to reflect the response of glioma patients to immunotherapy. In this study, we aimed to assess the clinical predictive value of ITGB2 in patients with glioma.

Methods: The correlation between ITGB2 expression levels and glioma progression was explored and validated using data from CGGA, TCGA, GEO datasets, and patient samples from our hospital. Univariate and multivariate cox regression models were developed to determine the predictive role of ITGB2 on the prognosis of patients with glioma. The relationship between ITGB2 and immune activation was then analyzed. Finally, we predicted the immunotherapy response in both high and low ITGB2 expression subgroups.

Results: ITGB2 was significantly elevated in gliomas with higher malignancy and predicted poor prognosis. In multivariate analysis, the hazard ratio for ITGB2 expression (low versus high) was 0.71 with 95% CI (0.59-0.85) (P < 0.001). Furthermore, we found that ITGB2 stratified glioma patients into high and low ITGB2 expression subgroups, exhibiting different clinical outcomes and immune activation status. At last, we demonstrated that glioma patients with high ITGB2 expression levels had better immunotherapy response.

Conclusions: This study demonstrated ITGB2 as a novel predictor for clinical prognosis and response to immunotherapy in gliomas. Assessing expression levels of ITGB2 is a promising method to discover patients that may benefit from immunotherapy.

Keywords: Biomarker; Gliomas; ITGB2; Immune activation; Immunotherapy; T cell.

MeSH terms

  • Biomarkers, Tumor*
  • Brain Neoplasms / etiology
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / mortality*
  • Brain Neoplasms / therapy
  • Computational Biology / methods
  • Databases, Genetic
  • Disease Progression
  • Gene Expression Profiling
  • Glioma / diagnosis*
  • Glioma / metabolism*
  • Glioma / mortality
  • Glioma / therapy
  • Humans
  • Integrin beta1 / genetics
  • Integrin beta1 / metabolism*
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Neoplasm Grading
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Prognosis
  • Proportional Hazards Models
  • Transcriptome
  • Tumor Microenvironment / genetics
  • Tumor Microenvironment / immunology
  • Tumor-Associated Macrophages / immunology
  • Tumor-Associated Macrophages / metabolism

Substances

  • Biomarkers, Tumor
  • Integrin beta1
  • Itgb1 protein, human