Project summary:
The importance of T cells is well established in colorectal cancer, as their abundance in tumours predicts a good outcome in cancer patients. However, for the largest group of colorectal cancers – the microsatellite stable (MSS) group, which represents 80-85% of cases – T cells are largely absent from tumours. Patients with MSS tumours respond poorly to T cell checkpoint inhibitors, such as anti-PD-1. Thus, a greater understanding of how T cells are excluded from MSS tumours is required. Across the genomic landscape of MSS tumours, mutations in WNT/beta-catenin-related genes are the strongest correlative of low T cell infiltration. Thus, the overall goal of this proposal is to mechanistically dissect the interaction between WNT/beta-catenin signalling, immunosurveillance and immune escape in colon cancer. This proposal will specifically focus on intraepithelial lymphocytes (IELs), a group of gut-resident, unconventional T cells consisting of both alpha/beta T cells and gamma/delta T cells, rather than conventional, dendritic cell-educated CD8+ T cells. The Coffelt lab has discovered that IELs recognize and kill pre-cancerous gut epithelial cells. We have found that WNT signalling negatively regulates T cell interacting molecules, but downregulation of these proteins is reversible if WNT signalling is inhibited.
Project Q&A Session
Friday 9th December, 1400 hrs.
ZOOM Meeting
https://uofglasgow.zoom.us/j/84193295568?pwd=YlBDLzFVVVMyQUtrRGFYRXFiTnpMZz09
Email: [Email Address Removed] for password information.
About the Programme
This MRC programme is joint between the Universities of Edinburgh and Glasgow. You will be registered at the host institution of the primary supervisor detailed in your project selection.
All applications should be made via the University of Edinburgh, irrespective of project location. For those applying to a University of Glasgow project, your application along with any supporting documents will be shared with University of Glasgow.
How to Apply: https://www.gla.ac.uk/colleges/mvls/graduateschool/mrcdtpprecisionmedicine/howtoapply/
Please note, you must apply to one of the projects and you must contact the primary supervisor prior to making your application. Additional information on the application process is available here: http://www.ed.ac.uk/studying/postgraduate/degrees/index.php?r=site/view&id=919
For more information about Precision Medicine visit:
http://www.ed.ac.uk/usher/precision-medicine
Application Enquiries
Alexis Merry
[Email Address Removed]
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