ARID1A, ARID1B, and ARID2 Mutations Serve as Potential Biomarkers for Immune Checkpoint Blockade in Patients With Non-Small Cell Lung Cancer

Front Immunol. 2021 Aug 26:12:670040. doi: 10.3389/fimmu.2021.670040. eCollection 2021.

Abstract

Worldwide, non-small cell lung cancer (NSCLC) has the highest morbidity and mortality of all malignancies. The lack of responsiveness to checkpoint inhibitors is a central problem in the modern era of cancer immunotherapy, with the rapid development of immune checkpoint inhibitors (ICIs) in recent years. The human switch/sucrose nonfermentable (SWI/SNF) chromatin-remodeling complex has been reported to be recurrently mutated in patients with cancer, and those with SWI/SNF mutations have been reported to be sensitive to ICIs. Six reported cohorts, a total of 3416 patients, were used to analyze the mutation status of ARID1A, ARID1B, ARID2 and SMARCA4 in patients with NSCLC and the effect of mutations on prognosis after ICIs. Finally, a nomogram was established to guide the clinical use of ICIs. The results show that patients with NSCLC who have ARID1A, ARID1B, and ARID2 mutations of the SWI/SNF complex were more likely to benefit from ICI therapy.

Keywords: PD-1/PD-L1 inhibitors; SWI/SNF complex; anti-PD1/PD-L1; immunotherapy; non-small cell lung cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / immunology
  • Clinical Decision-Making
  • DNA Mutational Analysis
  • DNA-Binding Proteins / genetics*
  • Decision Support Techniques
  • Female
  • Humans
  • Immune Checkpoint Inhibitors / therapeutic use*
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / immunology
  • Male
  • Middle Aged
  • Mutation*
  • Nomograms
  • Patient Selection
  • Predictive Value of Tests
  • Transcription Factors / genetics*
  • Treatment Outcome
  • Tumor Microenvironment

Substances

  • ARID1A protein, human
  • ARID1B protein, human
  • ARID2 protein, human
  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • Immune Checkpoint Inhibitors
  • Transcription Factors