Macrophage driven therapy resistance in AML: from macrophage subset characterisation to the potential for therapeutic intervention

Resistance to cancer drugs or therapy resistance, is a major reason for treatment failure, disease recurrence, and poor survival in acute myeloid leukaemia (AML); a common blood cancer in adults, with 1 in 5 patients surviving for 5 years or more after diagnosis. Communication between blood cancer cells, and other cells present within the bone marrow, significantly contribute towards therapy resistance. Immune cells called “macrophages”, and in particular cancer-supporting subtypes of macrophages, are present in high numbers in the bone marrow of blood cancer patients, including AML and multiple myeloma. These macrophages are known to contribute towards therapy resistance in multiple myeloma. It is important that we identify macrophage subtypes that are capable of driving therapy resistance in AML, in order to explore their potential to be targeted by new or existing drug treatments. My research findings provide an important breakthrough in this poorly-understood field of research, by showing that macrophages protect blood cancer cells from the killing effects of cancer drugs, through physical cell-to-cell contact between blood cancer cells and macrophages, and/or factors released by these macrophages. Additionally, factors released by macrophages, activate important pro-survival pathways in blood cancer cells.

This project will use advanced cell-sorting, and cell and molecular biology techniques, to understand the importance of specific macrophage subtypes in therapy resistance, providing a major advance in our understanding of how macrophages impact upon this disease process. These findings will inform future studies, exploring the potential of specific macrophage subtypes, as therapeutic targets to treat blood cancers.