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A pan-cancer gamma delta T cell repertoire

Yu, X.; Song, L.; Cen, L.; Cao, B.; Tao, R.; Shen, Y.; Abate-Daga, D.; Rodriguez, P. C.; Conejo-Garcia, J. R.; Wang, X.

2024-07-22 genomics
10.1101/2024.07.18.604205 bioRxiv
Show abstract

This report presents the largest collection of gamma-delta T cell receptor ({gamma}{delta} TCR) reads in human cancer to date, analyzing about 11,000 patient tumor samples across 33 cancer types using the TRUST4 algorithm. Despite {gamma}{delta} T cells being a small fraction of the T cell population, they play a key role in both innate and adaptive immunity. Our comprehensive analysis reveals their significant presence across all cancer types, specifically highlighting the diverse spectrum and clonality patterns of their {gamma}{delta} receptors. This research highlights the complex roles of {gamma}{delta} T cells in tumor tissues and their potential as prognostic biomarkers. We also demonstrate the utility of T cell receptor gamma (TRG) and delta (TRD) gene expression values from standard RNA-seq data. Ultimately, our work establishes a fundamental resource for future tumor-infiltrating {gamma}{delta} T cell research and may facilitate the development of novel {gamma}{delta}-T-cell-based therapeutic strategies. Together, we demonstrate the strong diversity and prognostic potential of {gamma}{delta} T cells in multiple cancer types. HighlightsComprehensive analysis of {gamma}{delta} TCRs from 11,473 tumor samples Significant variability and overall consistency in {gamma}{delta} gene expression and clonotype {gamma}{delta}TCR expression and diversity as prognostic biomarkers across multiple cancers Centralized {gamma}{delta} TCR repertoire database for future therapeutic discovery

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