M2-polarized macrophages control LSC fate by enhancing stemness, homing, immune evasion and metabolic reprogramming [article]

Isabel Weinhauser, Diego Pereira-Martins, Luciana Almeida, Jacobien Hilberink, Cesar Ortiz, Douglas Silveira, Lynn Quek, Cleide Araujo, Thiago Bianco, Antonio Lucena-Araujo, Nienke Visser, Shanna Hogeling (+5 others)
2022 bioRxiv   pre-print
While it is increasingly becoming clear that cancers are a symbiosis of diverse cell types and tumor clones, the tumor microenvironment (TME) in acute myeloid leukemias (AML) remains poorly understood. Here, we uncover the functional and prognostic relevance of an M2-polarized macrophage compartment. Intra bone marrow co-injection of M2d-macrophages together with leukemic blasts that fail to engraft on their own now induce fatal leukemia in mice. Even a short-term two-day in vitro exposure to
more » ... d macrophages can 'train' leukemic blasts after which cells are protected against phagocytosis, display increased mitochondrial metabolism and improved in vivo homing, resulting in full-blown leukemia. We developed an M2d-based biomarker panel that outperforms currently used AML prognosis predictors. Our study provides insight into the mechanisms by which the immune landscape contributes to aggressive leukemia development and provides alternatives for effective targeting strategies.
doi:10.1101/2022.05.06.489506 fatcat:z6mtijjsjngwzp5hlye3uc36zm