ArticleTranslational cancer research2026
Characterizing immune heterogeneity in gastric cancer by high-throughput T-cell receptor sequencing: predictive clonotypes and functional signatures.
Article in Translational cancer research, 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: Gastric cancer (GC) exhibits significant immunological heterogeneity, posing a major challenge for achieving durable responses to immunotherapy. Robust immune biomarkers for predicting treatment efficacy need to be identified. T-cell receptor (TCR) repertoire profiling has emerged as a promising approach for characterizing anti-tumor immune dynamics and therapeutic responsiveness. The aim of this study was to characterize immune heterogeneity in gastric cancer by high-throughput TCR sequencing and identify predictive clonotypes and functional signatures. Methods: High-throughput single-cell T-cell receptor beta (TCRβ) sequencing was performed on 89 longitudinal peripheral blood samples collected from 23 GC patients undergoing immunotherapy. TCR repertoire features, including diversity indices, clonal architecture, V-J gene usage, and complementarity-determining region 3 (CDR3) sequence characteristics, were systematically analyzed. The patients were stratified based on dynamic changes in TCR diversity during treatment. Results: Based on TCR diversity dynamics, the patients were classified into three TCR diversity dynamic patterns: sustained high-diversity, diversity-declining pattern, and fluctuating-diversity pattern. An early decline in clonal richness, as measured by the Chao1 index, was associated with subsequent treatment resistance. The responders showed pronounced oligoclonal T-cell expansion, while the non-responders showed polyclonal dispersion. A conserved V-J gene pairing ( Conclusions: Distinct TCR repertoire characteristics are closely associated with immunotherapy outcomes in GC. Early changes in TCR diversity and the presence of public clonotype-like features may represent candidate biomarkers of therapeutic efficacy that warrant validation in larger cohorts. These findings provide an exploratory basis for future development of TCR-based response monitoring strategies and for further investigation of personalized immunotherapeutic approaches.
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