Abstract
BackgroundKnowledge of immune cell phenotypes, function, and developmental trajectory in acute myeloid leukemia (AML) microenvironment is essential for understanding mechanisms of evading immune surveillance and immunotherapy response of targeting special microenvironment components.MethodsUsing a single-cell RNA sequencing (scRNA-seq) dataset, we analyzed the immune cell phenotypes, function, and developmental trajectory of bone marrow (BM) samples from 16 AML patients and 4 healthy donors, but not AML blasts.ResultsWe observed a significant difference between normal and AML BM immune cells. Here, we defined the diversity of dendritic cells (DC) and macrophages in different AML patients. We also identified several unique immune cell types including T helper cell 17 (TH17)-like intermediate population, cytotoxic CD4+ T subset, T cell: erythrocyte complexes, activated regulatory T cells (Treg), and CD8+ memory-like subset. Emerging AML cells remodels the BM immune microenvironment powerfully, leads to immunosuppression by accumulating exhausted/dysfunctional immune effectors, expending immune-activated types, and promoting the formation of suppressive subsets.ConclusionOur results provide a comprehensive AML BM immune cell census, which can help to select pinpoint targeted drug and predict efficacy of immunotherapy.
Highlights
Knowledge of immune cell phenotypes, function, and developmental trajectory in acute myeloid leukemia (AML) microenvironment is essential for understanding mechanisms of evading immune surveillance and immunotherapy response of targeting special microenvironment components
Myeloid-derived suppressor cells (MDSCs)-like cells expanded in AML patients [26], but its heterogeneity and features of developmental trajectory do not benefit for screening effective specific targets, which should be identified by scRNA-seq analysis and meticulous functional assay
A scRNA-seq census of AML bone marrow (BM) immune cells pre- and post-treatment We hypothesized the immune phenotypes and status were remodeled by uncontrollable AML blasts, it might be identifiable in data generated from recent efforts to distinguish AML hierarchies [32]
Summary
Knowledge of immune cell phenotypes, function, and developmental trajectory in acute myeloid leukemia (AML) microenvironment is essential for understanding mechanisms of evading immune surveillance and immunotherapy response of targeting special microenvironment components. MDSC-like cells expanded in AML patients [26], but its heterogeneity and features of developmental trajectory do not benefit for screening effective specific targets, which should be identified by scRNA-seq analysis and meticulous functional assay. AML blasts can systematically change the immune status of BM microenvironment to support malignant cell growth and resist immune surveillance
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