Do chronic myeloid leukaemia stem cells actively evade the host immune response?

Dr Alison Michie, University of Glasgow

Tumour cells, like viruses, have developed mechanisms to assist in their ability to evade host immune surveillance in order to promote cancer development and expansion.  This can occur by modifying their ability to be identified by the host immune cells, or by manipulating the surrounding tumour tissue to subvert immune cells away from a tumour cell-directed killing response. This results in the tumour cells surviving in the host, thus being able to cause a relapse. In Chronic Myeloid Leukaemia (CML), while patients possess cells that are capable of recognising leukaemic cells, the immune response mounted is limited. This suggests that CML cells can either directly or indirectly manipulate the host immune response.

Dr Michie and her team have preliminary data demonstrating that CML stem cells specifically reduce sensitivity of MHC class II, a cell surface receptor responsible for activating a specific cellular component of the immune system. This suggests that CML stem cells escape immune surveillance by subverting the immune response of leukaemia-specific cells.

The funding provided by Leuka has enabled an exciting new collaboration to be formed within the University of Glasgow between immunology (Alison M. Michie), haematology (Tessa L. Holyoake) and epigenetics (David Vetrie) to explain the cellular and molecular mechanisms that regulate the immune subversion in CML stem cells.  

The team's aim is to determine whether the reduced sensitivity of MHC class II is the mechanism employed to assist CML stem cells to evade the immune system. The findings associated with this project could lead to the inclusion of immunomodulatory therapies for CML patients, to make CML stem cells more visible to the host immune cells. In this way, it would be possible to deliver a longterm remission or cure for patients diagnosed with CML. 

We are extremely grateful to Leuka for giving us this opportunity to address this important research question, which may have implications for developing immunotherapy-based treatments for other leukaemias and solid tumours.

Dr Alison Michie