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Predictive value of TCR Vβ-Jβ profile for adjuvant gefitinib in EGFR mutant NSCLC from ADJUVANT-CTONG 1104 trial
Cunte Chen, … , Si-Yang Liu, Yangqiu Li
Cunte Chen, … , Si-Yang Liu, Yangqiu Li
Published January 11, 2022
Citation Information: JCI Insight. 2022;7(1):e152631. https://doi.org/10.1172/jci.insight.152631.
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Research Article Oncology

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

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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.

Authors

Cunte Chen, Si-Yang Maggie Liu, Yedan Chen, Qiuxiang Ou, Hua Bao, Ling Xu, Yikai Zhang, Wenzhao Zhong, Qing Zhou, Xue-Ning Yang, Yang Shao, Yi-Long Wu, Si-Yang Liu, Yangqiu Li

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Figure 1

Study schematics.

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Study schematics.
Patients from the ADJUVANT-CTONG 1104 trial with stage...
Patients from the ADJUVANT-CTONG 1104 trial with stage II/III NSCLC with an epidermal growth factor receptor (EGFR) mutation were divided into 2 cohorts to receive the EGFR tyrosine kinase inhibitor gefitinib (TKI-Gefitinib) or vinorelbine/cisplatin (Chemo-VP) treatment. The paraffin-preserved pretreatment tumor and tumor-adjacent tissues of patients in the TKI-gefitinib and Chemo-VP cohorts were collected and fractionated for DNA analysis and multiplex PCR for β chain T cell receptor (TCRβ) sequencing. Correlations between the TCR repertoire and clinical outcomes were explored.

Copyright © 2023 American Society for Clinical Investigation
ISSN 2379-3708

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