Molecular Horizons PhD Exit Seminar

Donor stem cell transplantation (SCT) is the only curative therapy for blood cancers such as lymphoma and leukaemia. However, 50% of all SCT recipients develop deadly graft-versus-host disease (GVHD). GVHD is an inflammatory disease that is lethal in 15% of sufferers and occurs when donor immune cells in the SCT (graft) become reactive against the recipient (host). This causes severe damage to host tissue, including the liver, small-intestines and skin. Current treatments for GVHD are extremely limited and have life-threatening side-effects. Therefore, my PhD thesis aims to identify new therapeutic strategies against GVHD by specifically targeting the donor immune cells that propagate the disease. These strategies were tested in a humanised mouse model of GVHD, where immunodeficient mice are injected with human immune cells.

My research has explored how single nucleotide polymorphisms in donor genes important in inflammation can influence GVHD development. Moreover, I have examined how depletion of reactive donor immune cells with post-transplant cyclophosphamide (PTCy) reduces GVHD in this model.

Finally, I have investigated how combinational therapy involving PTCy influences GVHD. This seminar will present these findings, including flow cytometric analysis of human immune cell populations, clinical assessment of GVHD development and the expression of different inflammatory markers in this humanised mouse model.