Work

Biased monocyte subsets contribute to acute myeloid leukemia 3204

Year: 2025

Type: article

Abstract: Description Monocytes are essential for innate immunity, classified into Classical and Non-Classical subtypes with roles in inflammation. In cancer, monocytes impair immune responses through dysfunctional phagocytosis, cytokine secretion, and macrophage maturation. Acute Myeloid Leukemia (AML) disrupts marrow function, impeding immune cell differentiation, however, the impact on monocytes remains unknown. Our study investigates monocyte dysfunction during AML progression, hypothesizing that AML-induced inflammation shifts monocyte subsets across hematopoietic tissues. To test this, we developed a novel chimeric AML mouse model to distinguish host-derived monocytes from leukemic blasts via CD45 expression, enabling in-depth analysis through flow cytometry. Our results revealed a decrease in marrow-resident monocytes and an increase in splenic monocytes. Additionally, Classical monocytes were depleted in both spleen and peripheral blood, while Non-Classical monocytes expanded. We also observed an increase in chimeric, non-transformed myeloid progenitor cells, indicating that leukemic blasts influence monocyte differentiation. This shift likely contributes to an immunosuppressive tumor microenvironment, hindering immune responses and complicating therapy. These findings underscore monocyte dysfunction as a significant contributor to immune evasion in AML and suggest targeting monocyte subsets as a potential therapeutic strategy to restore immune function in hematological malignancies. Funding Sources Supported by ACS DICR Fellowship Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)

Source: The Journal of Immunology

DOI: 10.1093/jimmun/vkaf283.1029