Kennedy Trust Prize Studentships
Investigating the CD8 T cell subsets responding to cancer immunotherapy
Checkpoint blockade is a type of immunotherapy that has shown unprecedented success in treating highly aggressive cancers, particularly blockade of the protein called programmed cell death–1 (PD-1). Checkpoint blockade act by reinvigorating T cells that have been inhibited by the tumour (“exhausted” T cells), enabling T cell killing capacities and destruction of the tumour. Although responding patients often show long-term remission, the response rates to these therapies are only 15 to 30%. Several factors have been correlated with the response to checkpoint blockade but they fail to predict which patient will respond. Predictive biomarkers are therefore still missing, in part because there is only a partial understanding of the mechanisms of sensitivity or resistance to immunotherapy. This project will investigate the CD8 T cell response to anti-PD-1 immunotherapy in space and time. We will use our expertise in cutting edge microscopy (1-3) and tumour immunology (3) to analyse the dynamics and phenotype of CD8 T cells reinvigorated by immunotherapy. We will incorporate functional reporters, phenotyping and genomics to evaluate the responding CD8 T cell subsets. These studies will analyse the microenvironment fostering CD8 T cell response to anti-PD-1 therapy and identify whether a specific T cell subset is required for tumour clearance.
The Kennedy Institute is a world-renowned research centre and is housed in a brand new state-of-the-art research facility. Full training will be provided in a range of cell and molecular biology techniques, and imaging. A core curriculum of 20 lectures will be taken in the first term of year 1 to provide a solid foundation in immunology and data analysis. Students will attend weekly departmental meetings and will be expected to attend seminars within the department and those relevant in the wider University. Students will also attend external scientific conferences where they will be expected to present the research findings.
(1) Secondary T cell-T cell synaptic interactions drive the differentiation of protective CD8+ T cells. Gérard A. et al, (2013), Nat Immunol, 14, 356 – 363.
(2) Detection of rare antigen-presenting cells through T cell-intrinsic meandering motility, mediated by Myo1g. Gérard A. et al, (2014), Cell, 158, 492 – 505.
(3) Visualization of Immediate Immune Responses to Pioneer Metastatic Cells in the Lung, Mark B. Headley. et al. Nature 2016 Mar 24;531(7595):513-7.
- Tumour Immunology
- Adaptive Immunity
Contact: Dr Audrey Gérard, Kennedy Institute, University of Oxford