About Dr Mark Williams

Allogeneic haematopoietic stem cell transplantation is the only curative therapy for many patients with acute myeloid leukaemia (AML) and other poor-risk haematological malignancies. Recipients are ‘conditioned’ with chemo/radiotherapy before receiving blood-forming stem cells harvested from a donor. These stem cells repopulate the bone marrow and provide a new immune system, which eliminates the cancer. However, disease relapse remains the most common cause of death and is due to failure of donor T cells to eliminate residual leukaemia in some cases. Donor T cells are often dysfunctional at relapse and leukaemic cells frequently exhibit reduced immunogenicity. 

In the Leukaemia Immunology and Transplantation laboratory, we aim to develop a comprehensive strategy to prevent post-transplant relapse. We are developing novel biomarkers to identify patients at risk of relapse, defining the critical drivers of T-cell dysfunction and exploring the potential of pharmacological induction of leukaemic differentiation to augment donor T-cell responses. 

We also aim to address fundamental questions of leukaemia immunology. Recent advances in cancer immunotherapy have yet to benefit patients with AML and understanding this failure is necessary to inform novel approaches. The basis of contemporary immunotherapy is that tumours elicit T-cell responses which they must then evade. Restoring or enhancing these responses is a key therapeutic goal that is exemplified by the success of immune checkpoint inhibitors. However, these treatments have not improved outcomes in AML, despite allogeneic stem cell transplantation demonstrating the curative potential of leukaemia-reactive T cells. It remains unclear whether AML elicits robust autologous T-cell responses and addressing this question is a key aim of the group.