Specific TCR profiles predict clinical outcome of adjuvant EGFR-TKIs for resected EGFR-mutant non-small cell lung cancer

• Published in: Biomarker research Vol. 11; no. 1; pp. 26 - 5
• Main Authors: Liu, Si-Yang Maggie, Chen, Cunte, Zhang, Yi-Kai, Zhong, Wen-Zhao, Wu, Yi-Long, Liu, Si-Yang, Li, Yangqiu
• Format: Journal Article
• Language: English
• Published: London BioMed Central 07.03.2023; BioMed Central Ltd; BMC
• Subjects: Adjuvant EGFR-TKI; Adjuvant treatment; Antigens; Biomarkers; Biomedical and Life Sciences; Biomedicine; Cancer; Cancer Research; Cancer therapies; Chemotherapy; Correspondence; CTONG1104; EGFR mutation; Epidermal growth factor receptors; Gefitinib; Genetic diversity; Immunotherapy; Lung cancer; Lung cancer, Non-small cell; Lung cancer, Small cell; Lymphocytes; Medical prognosis; Mutants; Mutation; Non-small cell lung cancer; Non-small cell lung carcinoma; Patient outcomes; Patients; Prediction models; Prognosis; Small cell lung carcinoma; Survival analysis; T cell receptors; T cells; T-cell receptor repertoire; Tumors; Vβ7-3Jβ2-5/Vβ24-1Jβ2-1/Vβ28Jβ2-2/Vβ5-6Jβ2-7; mutation; Vβ7-3Jβ2-5/Vβ24-1Jβ2-1/Vβ28Jβ2-2/Vβ5-6Jβ2-7; T-cell receptor repertoire; CTONG1104; Adjuvant EGFR-TKI; Non-small cell lung cancer; EGFR mutation
• ISSN: 2050-7771; 2050-7771
• DOI: 10.1186/s40364-023-00470-z

Background ADJUVANT-CTONG1104 reported a favorable survival outcome from adjuvant gefitinib treatment over chemotherapy in EGFR -mutant non-small cell lung cancer (NSCLC) patients. However, heterogeneous benefit from EGFR-TKIs and chemotherapy demands further biomarker exploration for patient selection. Previously, we identified certain TCR sequences with predictive value for adjuvant therapies from the CTONG1104 trial and found a relationship between the TCR repertoire and genetic variations. It remains unknown which TCR sequences could further enhance the prediction for only adjuvant EGFR-TKI. Methods In this study, 57 tumor and 12 tumor-adjacent samples, respectively, from gefitinib-treated patients in the CTONG1104 were collected for TCR β gene sequencing. We attempted to constitute a predictive model for prognosis and favorable adjuvant EGFR-TKI outcome for patients with early-stage NSCLC and EGFR mutations. Results The TCR rearrangements demonstrated significant prediction for overall survival (OS). A combined model of high frequent Vβ7-3Jβ2-5 and Vβ24-1Jβ2-1 with lower frequent Vβ5-6Jβ2-7 and Vβ28Jβ2-2 constituted the best value for predicting OS ( P  < 0.001; Hazard Ratio [HR] = 9.65, 95% confidence interval [CI]: 2.27 to 41.12) or DFS ( P  = 0.02; HR = 2.61, 95% CI: 1.13 to 6.03). In Cox regression analyses, when multiple clinical data were included, the risk score remained an independent prognostic predictor for OS ( P  = 0.003; HR = 9.49; 95% CI: 2.21 to 40.92) and DFS ( P  = 0.015; HR = 3.13; 95% CI: 1.25 to 7.87). Conclusions In this study, a predictive model was constituted with specific TCR sequences for prognosis prediction and gefitinib benefit in the ADJUVANT-CTONG1104 trial. We provide a potential immune biomarker for EGFR -mutant NSCLC patients who might benefit from an adjuvant EGFR-TKI.