Donor/allogeneic stem cell transplantation (allo-SCT) is a vital therapeutic intervention in which hematopoietic stem cells from a genetically distinct, HLA-compatible donor are infused into a recipient to treat both malignant and non-malignant haematological conditions. This procedure aims to restore the recipient's hematopoietic and immune systems and provide anti-tumour immunity via graft-versus-leukemia (GVL) effects, with potentially curative outcomes. However, treatment failure is common, such as relapse of the underlying malignancy, which underscores the need for close monitoring and potential adjuvant therapies.
Graft-versus-host disease (GVHD) also constitutes a significant challenge, as donor-derived immune cells attack recipient tissues, causing multi-organ dysfunction and significant increased morbidity and mortality. Notably however, GVHD's immunological response may confer a collateral GVL effects, wherein donor-derived immune cells target residual malignant host cells and reduce the risk of relapse. Patients may also experience increased susceptibility to infections due to a weakened immune system resulting from chemotherapy and/or radiation therapy conditioning regimens, and immune dysfunction during immune reconstitution and GVHD.
New therapeutics to manage these complications are essential for optimizing transplant outcomes and patient quality of life. Given the importance of T cells in driving GVHD, anti-tumour immunity and infection control we have focussed our efforts to understand pathogenic and protective T cell developmental pathways in the context of allo-SCT.
Here I will present our recent data examining the influence of allo-SCT in re-shaping the human CD8+ T cell compartment over time, as well as preclinical data investigating the effects of modulating upstream regulators of pro-inflammatory allogeneic T cells on GVHD