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Significant differences in T cell receptor repertoires in lung adenocarcinomas with and without epidermal growth

Eisaku Miyauchi1,2, Tatsuo Matsuda1, Kazuma Kiyotani3

  • 1Department of Medicine, The University of Chicago, Chicago, Illinois.

Cancer Science
|December 25, 2018
PubMed

Insights

Patients with EGFR-mutant lung cancer show poorer outcomes with immune checkpoint inhibitors. This study found EGFR mutations are linked to altered T cell receptor repertoires and fewer neoantigens, explaining immune resistance.

Area of Science:

  • Oncology
  • Immunology
  • Genetics

Background:

  • Immune checkpoint inhibitors (ICIs) show varied efficacy in non-small cell lung cancer (NSCLC).
  • Patients with epidermal growth factor receptor (EGFR) mutations often experience worse outcomes with ICIs.
  • The mechanisms underlying EGFR mutation-associated immune resistance are not fully understood.

Purpose of the Study:

  • To investigate T cell receptor (TCR) repertoire characteristics in lung adenocarcinoma with and without EGFR mutations.
  • To explore the relationship between EGFR mutation status, TCR repertoire, and tumor mutational landscape.

Main Methods:

  • Collected 39 paired lung adenocarcinoma tissues (20 with EGFR mutations).
  • Performed TCR repertoire analysis, whole-exome sequencing (WES), and transcriptome analysis.
  • Analyzed TCR diversity, non-synonymous mutations, and predicted neoantigens.

Main Results:

  • EGFR-mutant tumors exhibited significantly higher TCR diversity compared to wild-type tumors, indicating lower T cell clonal expansion.
  • EGFR-mutant tumors had fewer non-synonymous mutations and predicted neoantigens than wild-type tumors.
  • A positive correlation was observed between non-synonymous mutations and TCRβ clonotype frequencies.

Conclusions:

  • Significant differences exist in TCR repertoires and neoantigen load between EGFR-mutant and wild-type lung tumors.
  • These findings provide insights into the molecular mechanisms of immune resistance in EGFR-mutant NSCLC.
  • Understanding these differences may guide the development of targeted immunotherapies for specific patient subgroups.
Keywords:
EGFR mutationT cell receptor repertoirelung adenocarcinomaneoantigennon-synonymous mutation

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