Modulators of T Cell Function in Cancer Immunotherapy

Supervisors: Dr Rasha Abu Eid (Institute of Dentistry), Dr Frank Ward (Institute of Medical Sciences) and Dr Raif Yuecel (Institute of Medical Sciences)

Cancer immunotherapy is among the most important developments in cancer treatment. Despite its impressive successes, the response in patients is often limited and short lived. This is due to factors that hamper the immune response against tumour cells.

Regulatory CD4 T-cells (Tregs) are major contributors to the suppressive tumour microenvironments and immune modulators that selectively mitigate these cells are needed.

The expression of co-inhibitory molecules by tumour cells is another tumour mediated immune escape mechanism that leads to the suppression of effector T-cells. Immune checkpoint inhibitors that block the interaction between these co-inhibitory molecules and their receptors have shown remarkable results in enhancing anti-tumour therapeutic efficacy.

Additionally, cancer immunotherapy is hindered by the short-lived anti-tumour effect due to the exhaustion of tumour-specific effector CD8 T-cells. The phenotype and differentiation status of CD8 T-cells have major influences on their function. There is intense interest in manipulating immune modulators to maximise their cytotoxicity and enhance their longevity as part of cancer immunotherapy.

Small molecule inhibitors that target different signalling pathways within T cells have been used successfully to modulate T-cell responses by selectively inhibiting Tregs and/or generating superior antigen-specific CD8 T-cells with enhanced proliferative ability, survival and functional capability. Furthermore, immune checkpoint inhibitors have proven successful in modulating the anti-tumour immune response.

The aim of this project is to identify targets for selective modulation of immune cells while understanding the specific mechanisms that control T cell development and responses. Results will guide combination therapies with different immune modulators as part of cancer treatment.

This project provides exceptional opportunities for the student to benefit from diverse expertise and to be exposed to cutting edge techniques including flow cytometry, molecular biology, cell-culture, animal handling and imaging.

The student will engage in a novel translational area of research that will contribute to understanding cancer immunology and guiding the development of cancer immunotherapy.

Application:

Please select ’Degree of Doctor of Philosophy in Medical Sciences (Science)’ from the list of programme options in the University of Aberdeen’s online postgraduate applicant portal to ensure that your application is passed to the correct school for processing. Then manually enter the name of the supervisor(s), project title and funder (Elphinstone) in the space provided.