Abstract
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. β 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 Vβ-Jβ rearrangements were significantly associated with OS. Patients with a higher frequency of Vβ5-6Jβ2-1, Vβ20-1Jβ2-1, Vβ24-1Jβ2-1, and Vβ29-1Jβ2-7 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, Vβ5-6Jβ2-1, Vβ20-1Jβ2-1, and Vβ24-1Jβ2-1 had a significant relationship with gefitinib treatment, while Vβ29-1Jβ2-7 was associated with chemotherapy. Four TCR Vβ-Jβ 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.
Highlights
Precision therapy for non–small cell lung cancer (NSCLC) based on genetic alterations greatly changed clinical practice [1, 2]
Four T cell receptor (TCR) Vβ-Jβ rearrangements related to favorable overall survival (OS) and disease-free survival (DFS) for adjuvant gefitinib and chemotherapy in patients with an epidermal growth factor receptor (EGFR) mutation with stage II/III NSCLC; this may provide a novel perspective for the adjuvant setting for resectable NSCLC
High TCR clonality associated with favorable OS in patients with stage II/III NSCLC
Summary
Precision therapy for non–small cell lung cancer (NSCLC) based on genetic alterations greatly changed clinical practice [1, 2]. The FDA approved osimertinib for adjuvant therapy in patients with EGFR exon 19 deletions or exon 21 L858R mutations [11]. Despite the success of targeted therapy in EGFR mutant NSCLC, the heterogeneous outcomes suggest that the effects may not depend solely on EGFR-driven cancer cells, but may be associated with the local tumor immune microenvironment and antitumor T cell responses [12, 13]. The latter may be characterized through the distribution and diversity of T cell receptors (TCRs) [14]
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