MRC DTP in Precision Medicine

Mapping gamma delta T cells in colonic pre-malignancies

Supervisors

Prof Seth Coffelt, School of Cancer Sciences, University of Glasgow

Dr Philip Dunne, School of Cancer Sciences, University of Glasgow

Prof Joanne Edwards, School of Cancer Sciences, University of Glasgow

Prof Farhat Din, Clinical Surgery, University of Edinburgh

Summary

Colorectal cancer (CRC) develops through a well-characterised adenoma-carcinoma sequence, yet the immunological events governing early malignant transformation remain poorly understood. Gamma delta (γδ) T cells are unconventional lymphocytes that occupy the interface between innate and adaptive immunity, with particular enrichment at mucosal barrier sites such as the colonic epithelium. Despite their established roles in epithelial surveillance and anti-tumour immunity, their behaviour within pre-cancerous colonic adenomas has received little systematic investigation. This PhD project aims to characterise γδ T cells in human colonic adenomas with respect to their spatial distribution, phenotypic identity, and functional state. Using multiplex immunofluorescence and spatial transcriptomics, the project will map γδ T cell localisation across distinct tumour microenvironment compartments — epithelial, stromal, and immune niches — to determine whether spatial positioning correlates with discrete functional programmes. Complementary high-dimensional flow cytometry and single-cell RNA sequencing will resolve γδ T cell subsets, including Vδ1 and Vδ2 populations, and define their activation, cytotoxic, or regulatory phenotypes within the adenoma context. By integrating spatial and transcriptomic data, this work seeks to establish whether γδ T cells represent a meaningful immunosurveillance axis in early colorectal neoplasia, with implications for biomarker development and immunotherapeutic strategies targeting the adenoma-to-carcinoma transition.