Pan-cancer γδ TCR analysis uncovers clonotype diversity and prognostic potential

Summary

Gamma-delta T cells (γδ T cells) play a crucial role in both innate and adaptive immunity within tumors, yet their presence and prognostic value in cancer remain underexplored. This study presents a large-scale analysis of γδ T cell receptor (γδ TCR) reads from 11,000 tumor samples spanning 33 cancer types, utilizing the TRUST4 algorithm. Our findings reveal extensive diversity in γδ TCR clonality and gene expression, underscoring the potential of γδ T cells as prognostic biomarkers in various cancers. We further demonstrate the utility of TCR gamma (TRG) and delta (TRD) gene expression from standard RNA-sequencing (RNA-seq) data. This comprehensive dataset offers a valuable resource for advancing γδ T cell research, with implications for enhanced immunotherapy approaches or alternative therapeutic strategies. Additionally, our centralized database supports translational research into the therapeutic significance of γδ T cells.

Graphical abstract

Highlights

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  Comprehensive analysis of γδ TCRs from 11,473 tumor samples

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  Significant variability and overall consistency in γδ gene expression and clonotype

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  γδ TCR expression and diversity as prognostic biomarkers across multiple cancers

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  Centralized γδ TCR repertoire database for future therapeutic discovery

Abstract

Yu et al. present a large-scale analysis of gamma-delta T cell receptors spanning over 11,000 tumor samples. Their findings uncover the diversity and prognostic significance of these T cell subsets, highlighting their role in predicting cancer outcomes and offering insights for improving immunotherapy and advancing cancer research.