Identification of TCR rearrangements specific for genetic alterations in EGFR-mutated non-small cell lung cancer: results from the ADJUVANT-CTONG1104 trial

In this study, tumor tissues were collected from 101 patients with stage II/III resectable NSCLC with anEGFR mutation (57 patients were treated with gefitinib and 44 were treated with chemotherapy) in the ADJUVANT-CTONG1104 trial for high-throughput TCR β V region and exome sequencing. Ten clonal TCRs were associated withEGFR exon 19 deletion (del),EGFR exon 21 mutation (L858R),RB1 alteration,TP53 exon 4/5 missense mutation,TP53 nonsense mutation, or copy number gains inNKX2-1 andCDK4. Among the TCRs, there was frequent use of V β20-1Jβ2-3 specifically forEGFR exon 19 del or V β9Jβ2-1 specifically forEGFR exon 21 mutation (L858R), and these were significantly associated with favorable overall survival (OS) for NSCLC patients harboringEGFR exon 19 del or exon 21 L858R, particularly in the adjuvant gefitinib setting. Moreover, in comparison with the chemotherapy-preferable (CP) group, higher frequencies of V β20-1Jβ2-3 and Vβ9Jβ2-1 were found in the highly TKI-preferable (HTP) or TKI-preferable (TP) groups. Altogether, we identified ten TCR rearrangements specific for genetic alterations in NSCLC. Importantly, high abundance Vβ20-1Jβ2-3 or Vβ9Jβ2-1 may be an immune biomarker for guiding adjuvant gefitinib decisions for NSCLC patients harboringEGFR exon 19 del orEGFR exon 21 L858R.
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research