Summary
The induction of effective immune responses to tumours can provide long-lasting protection from cancer. In this regard, cytotoxic CD8+ T cells can suppress tumour growth by directly killing cancer cells and also by producing inflammatory cytokines. However, in many individuals the T cell response to cancer is ineffective. Several factors underlie the failure to mount protective immunity to cancer. Firstly, T cell responses can be suppressed by the inhibitory tumour environment. Secondly, tumour antigens are often perceived by the immune system as being identical to normal “self” tissue, and therefore a T cell response is not strongly induced. Therefore, it is clear that in order to improve patient outcomes and therapeutic opportunities in cancer, we need to understand how immune responses to tumours are regulated.
Full descriptionThe aim of this project is to investigate how T cells integrate antigenic, cytokine and environmental signals, particularly in the context of the tumour microenvironment. A key approach will be to determine how fundamental cellular metabolic pathways regulate T cell activation and effector function. This will be tested using in vitro and ex vivo analyses of transgenic mouse T cells. In vitro cellular immunology and biochemical techniques will complement in vivo mouse studies. A further aim to be to understand how these pathways are regulated in human T cells. This project is suitable for students with a strong background and interest in immunology, biochemistry, molecular biology or cell biology.
References:
- Salmond RJ, Brownlie RJ, Morrison VL, Zamoyska R. 2014. The tyrosine phosphatase PTPN22 discriminates weak self peptides from strong agonist TCR signals. Nat. Immunol. 15(9):875-883.
- Brownlie RJ, Garcia C, Ravasz M, Zehn D, Salmond RJ, Zamoyska R. 2017. Resistance to TGFβ suppression and improved anti-tumor responses in CD8+ T cells lacking PTPN22. Nat. Commun. 8(1):1343.