ArticleFrontiers in oncology2026
Dynamics of the immune repertoire in recurrent, locally advanced NSCLC not amenable for definitive therapy and in stage IV disease receiving first-line chemotherapy.
Article in Frontiers in oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Cytotoxic chemotherapy can modulate antitumor immunity, yet its impact on the peripheral T-cell receptor (TCR) repertoire in non-targetable advanced NSCLC remains poorly characterized. We prospectively investigated chemotherapy-induced TCRβ repertoire dynamics and their prognostic relevance. Methods: Patients with recurrent unresectable locally advanced or stage IV NSCLC without actionable mutations received first-line platinum-based chemotherapy (no immunotherapy) at Ramathibodi Hospital (2021-2024). Peripheral blood was collected at baseline (T1), chemotherapy completion (T2), and confirmed disease progression (T3). TCRβ sequencing (Ion Torrent™ Oncomine™ TCR Beta-LR) was performed on samples rarefied to >1.5 million reads. Shannon diversity, Pielou evenness, TCR convergence frequency, unique clone counts, and principal component analysis (PCA) of clonal frequencies were analyzed. Multiple comparisons were Benjamini-Hochberg corrected (significance: p<0.05, BH-adj. q<0.05). Results: Of 42 enrolled patients, 34 were T1-evaluable and 15 at T2; longitudinal attrition was driven primarily by pre-T2 death (74% vs. 27%; p=0.014). Disease control was achieved in 11/15 T2-evaluable patients (73%). Disease control patients trended higher TCR convergence (0.0040 vs. 0.0023) and significantly smaller decline in unique clone counts (-16% vs. -41%; Wilcoxon p=0.020, q=0.030). PCA revealed compact repertoire clustering in disease control versus wide PC2 dispersion in progressive disease (PD) patients (p=0.030, q=0.030). Among 4 patients reaching T3 (all PD), post-chemotherapy rises in Shannon diversity and convergence reversed at T3, consistent with immune attrition. Overall survival was significantly longer in disease control patients (log-rank p=0.036). Conclusion: Stable clonal convergence and preserved clone counts associate with disease control and survival in non-targetable advanced NSCLC receiving chemotherapy, supporting peripheral TCRβ profiling as an exploratory biomarker warranting prospective validation.
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