Paper on the role of macrophages in AML out now in Science Advances

Isabel and Diego functionally studied the role of the macrophage landscape in AML. It is increasingly becoming clear that cancers are a symbiosis of diverse cell types and tumor clones. Combined scRNAseq, flow cytometry and immunohistochemistry studies of the innate immune compartment in the bone marrow of AML patients reveal a shift towards a tumor-supportive M2-polarized macrophage landscape with an altered transcriptional program, with enhanced fatty acid oxidation and NAD+ generation. Functionally, these AML-associated macrophages display decreased phagocytic activity and intra bone marrow co-injection of M2-macrophages together with leukemic blasts strongly enhances in vivo transformation potential. A two-day in vitro exposure to M2 macrophages results in the accumulation of CALRlow leukemic blast cells, which are now protected against phagocytosis. Moreover, M2-exposed “trained” leukemic blasts display increased mitochondrial metabolism, in part mediated via mitochondrial transfer. Our study provides insight into the mechanisms by which the immune landscape contributes to aggressive leukemia development and provides alternatives for targeting strategies aimed at the tumor microenvironment.