Chronic exposure to tumour antigens in cancer and organ-specific antigens in autoimmune diseases such as type 1 diabetes (T1D) drives T cell exhaustion. T cell exhaustion reduces the effectiveness of T cells to control the tumours allowing cancer to progress, but paradoxically islet reactive T cells showing features of exhaustion continue to destroy beta-cells in T1D. Our work is focused on understanding how the exhausted T cells in the tumour environment are different to those developing in the autoimmune islet environment.

Understanding this will allow us to exploit processes that make T-cells causingT1D more exhausted like those in cancer and prevent T1D. To do this we have developed a novel transplantable tumour cell line expressing islet antigen(s). We will transplant tumours expressing islet antigens in the non-obese diabetic (NOD)mouse model of T1D and study the difference in the exhaustion program of islet antigen-specific T cells developing in the transplanted tumour and host islet microenvironment. We hypothesise that islet antigen-specific T cells infiltrating the tumour will undergo severe T cell exhaustion. To examine how exhausted islet-specific T cells regulate the other effector T cells in NOD mice we will remove the tumour and follow the NOD mice to see if they are protected from diabetes.

Supervised by

Gaurang Jhala

Research Officer, Immunology and Diabetes

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Available for Student Supervision