Leukaemia Immunology & Transplantation

We study a blood cancer treatment called allogeneic haematopoietic stem cell transplantation. This is a complex therapy that involves treating patients with chemo/radiotherapy before infusing blood-forming stem cells harvested from a donor. Donor immune cells then eliminate residual leukaemia, a process termed the graft-versus-leukaemia effect. Stem cell transplantation can cure patients with blood cancers that would recur if managed with chemotherapy alone, but disease relapse is common and remains the leading cause of death. We believe that a better understanding of how this treatment works and why it fails will improve transplant outcomes and inform the development of novel immunotherapies for blood cancers. 

Our group aims to understand and manipulate the graft-versus-leukaemia effect to reduce the risk of relapse and improve transplant outcomes. We also study fundamental questions of leukaemia immunology as these are critical to understanding how leukaemia cells interact with T cells and what determines the outcomes of these interactions. 

We are studying the T cells found in bone marrow at leukaemia diagnosis and following stem cell transplantation. We have used mass cytometry to profile millions of T cells from hundreds of patients and are currently determining the ability of various leukaemia-associated populations to recognise cancer cells. At disease presentation we aim to establish whether autologous T-cell responses to AML are common and robust enough to be manipulated for therapeutic effect. At post-transplant relapse we aim to determine why leukaemia-reactive T cells lose control of the disease by identifying drivers of T-cell dysfunction. 

AML is characterised by a block to differentiation leading to the accumulation of cancer cells that resemble myeloid stem and progenitor populations. Many recent and novel AML treatments work by releasing this block, leading to differentiation of leukaemia into mature myeloid cells, some of which are capable of presenting antigen to T helper cells. We are therefore investigating whether inducing leukaemic differentiation can support T-cell responses to clear the disease. Finally, we are developing novel biomarkers to predict the most serious transplant complications, namely disease relapse and graft-versus-host disease.