Predictive value of TCR Vβ-Jβ profile for adjuvant gefitinib in EGFR mutant NSCLC from ADJUVANT-CTONG 1104 trial

Herein, we characterize the landscape and prognostic significance of the T cell receptor (TCR) repertoire of early-stage non-small cell lung cancer (NSCLC) for patients with an epidermal growth factor receptor (EGFR) mutation. beta Chain TCR sequencing was used to characterize the TCR repertoires of paraffin-preserved pretreatment tumor and tumor-adjacent tissues from 57 and 44 patients with stage II/III NSCLC with an EGFR mutation treated with gefitinib or chemotherapy in the ADJUVANT-CTONG 1104 trial. The TCR diversity was significantly decreased in patients with an EGFR mutation, and patients with high TCR diversity had a favorable overall survival (OS). A total of 10 TCR V beta-J beta rearrangements were significantly associated with OS. Patients with a higher frequency of V beta 5-6J beta 2-1, V beta 20-1J beta 2-1, V beta 24-1J beta 2-1, and V beta 29-1J beta 2-7 had significantly longer OS. Weighted combinations of the 4 TCRs were significantly associated with OS and disease-free survival (DFS) of patients, which could further stratify the high and low TCR diversity groups. Importantly, V beta 5-6J beta 2-1, V beta 20-1J beta 2-1, and V beta 24-1J beta 2-1 had a significant relationship with gefitinib treatment, while V beta 29-1J beta 2-7 was associated with chemotherapy. Four TCR V beta-J beta rearrangements related to favorable OS and DFS for adjuvant gefitinib and chemotherapy in patients with an EGFR mutation with stage II/III NSCLC; this may provide a novel perspective for the adjuvant setting for resectable NSCLC.

Automated summary

In this study, the TCR repertoire of early-stage NSCLC patients with EGFR mutation was characterized, showing decreased diversity in patients with the mutation. High TCR diversity was associated with better overall survival, with specific TCR V beta-J beta rearrangements linked to longer survival. These findings suggest a potential novel perspective for adjuvant treatment in resectable NSCLC patients with EGFR mutation.