Rongqun Guo1, Mengdie Lü2, Fujiao Cao1, Guanghua Wu3, Fengcai Gao1, Haili Pang1, Yadan Li3,4, Yinyin Zhang1, Haizhou Xing1, Chunyan Liang1, Tianxin Lyu3,4, Chunyan Du5, Yingmei Li1, Rong Guo1, Xinsheng Xie1, Wei Li6, Delong Liu7, Yongping Song8, Zhongxing Jiang9. 1. Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. 2. Joint National Laboratory for Antibody Drug Engineering, Key Laboratory of Cellular and Molecular Immunology of Henan Province, Institute of Translational Medicine, School of Basic Medicine, Henan University, Kaifeng, Henan, China. 3. The Academy of Medical Science, College of Medical, Zhengzhou University, Zhengzhou, Henan, China. 4. The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan, China. 5. Laboratory Animal Center, School of Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China. 6. Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. zlyylw3028@zzu.edu.cn. 7. Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. delong_liu@nymc.edu. 8. Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. songyongping001@163.com. 9. Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. jiangzx@zzu.edu.cn.
Abstract
BACKGROUND: 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. METHODS: Using 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. RESULTS: We 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. CONCLUSION: Our results provide a comprehensive AML BM immune cell census, which can help to select pinpoint targeted drug and predict efficacy of immunotherapy.
BACKGROUND: 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. METHODS: Using 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 AMLpatients and 4 healthy donors, but not AML blasts. RESULTS: We observed a significant difference between normal and AML BM immune cells. Here, we defined the diversity of dendritic cells (DC) and macrophages in different AMLpatients. 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. CONCLUSION: Our results provide a comprehensive AML BM immune cell census, which can help to select pinpoint targeted drug and predict efficacy of immunotherapy.
Entities:
Keywords:
Acute myeloid leukemia; Bone marrow; Immune cells; Immune phenotypes; Microenvironment; Myeloid cells; Single-cell RNA sequencing; T lymphocytes
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