Research Projects

Chronic viral infections and cancers lead to dysfunctional CD8 T cells, characterised by high expression of the co-inhibitory checkpoint molecule PDI. Targeting PDI in immunotherapy has been successful in improving patient outcomes in cancer but there is a need to better understand the mechanisms that regulate CD8 T cell responses to improve immunotherapies. Recently, a subset of exhausted T cells that respond to checkpoint blockade were identified. This CD8 T cell subset resides in the T cell zone of the spleen and has unique features of stem-like cells. Also present in the spleen T cell zone are subsets of stromal cells that are required to orchestrate immune responses. By combining RNA sequencing with confocal microscopy and flow cytometry we identified dysfunctional changes in these stromal cells in the spleen. The aim of this project will be to understand how the spleen microenvironment, specifically the stromal cells, generate and maintain these stem-like virus-specific CD8 T cells in the context of chronic viral infection and B cell lymphoma. This project will provide new insights into the biology T cell dysfunction and open ways to generate better treatments for immunotherapy.

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