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

Cell Rep Med. 2024 Oct 15;5(10):101764. doi: 10.1016/j.xcrm.2024.101764. Epub 2024 Oct 4.

Abstract

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.

Keywords: T cell receptor; TCR clonality; TRUST4; cancer immunotherapy; gamma-delta T cells; immune repertoire; prognostic biomarkers.

MeSH terms

  • Clone Cells
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Intraepithelial Lymphocytes / immunology
  • Intraepithelial Lymphocytes / metabolism
  • Neoplasms* / genetics
  • Neoplasms* / immunology
  • Prognosis
  • Receptors, Antigen, T-Cell, gamma-delta* / genetics
  • Receptors, Antigen, T-Cell, gamma-delta* / immunology
  • Receptors, Antigen, T-Cell, gamma-delta* / metabolism
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism

Substances

  • Receptors, Antigen, T-Cell, gamma-delta