Use this URL to cite or link to this record in EThOS: | https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.726548 |
![]() |
|||||||
Title: | Evading the anti-tumour immune response : a novel role for Focal Adhesion Kinase | ||||||
Author: | Lund, Thomas Anthony |
ISNI:
0000 0004 6420 9866
|
|||||
Awarding Body: | University of Edinburgh | ||||||
Current Institution: | University of Edinburgh | ||||||
Date of Award: | 2016 | ||||||
Availability of Full Text: |
|
||||||
Abstract: | |||||||
Here I describe a new function of Focal Adhesion Kinase (FAK) in driving anti-tumour immune evasion. The kinase activity of FAK in squamous cancer cells drives the recruitment of regulatory T-cells (Tregs) by transcriptionally regulating chemokine/cytokine and ligand-receptor networks, including the transcription of CCL5 and TGFβ, which are required for enhanced Treg recruitment. In turn, these changes inhibit antigen-primed cytotoxic CD8+ T-cell activity in the tumour microenvironment, permitting survival and growth of FAK-expressing tumours. I show that immune evasion requires FAK’s catalytic activity, and a small molecule FAK kinase inhibitor, VS-4718, which is currently in clinical development, drives depletion of Tregs and permits CD8+ T-cell-mediated tumour clearance. It is therefore likely that FAK inhibitors may trigger immune-mediated tumour regression, providing previously unrecognized therapeutic benefit.
|
|||||||
Supervisor: | Frame, Margaret | Sponsor: | Medical Research Council (MRC) | ||||
Qualification Name: | Thesis (Ph.D.) | Qualification Level: | Doctoral | ||||
EThOS ID: | uk.bl.ethos.726548 | DOI: | Not available | ||||
Keywords: | Tregs ; T-cells ; Focal Adhesion Kinase ; FAK ; FAK inhibitors | ||||||
Share: |