Single-cell map of diverse immune phenotypes in the acute myeloid leukemia microenvironment

被引:73
作者
Guo, Rongqun [1 ]
Lu, Mengdie [2 ]
Cao, Fujiao [1 ]
Wu, Guanghua [3 ]
Gao, Fengcai [1 ]
Pang, Haili [1 ]
Li, Yadan [3 ,4 ]
Zhang, Yinyin [1 ]
Xing, Haizhou [1 ]
Liang, Chunyan [1 ]
Lyu, Tianxin [3 ,4 ]
Du, Chunyan [5 ]
Li, Yingmei [1 ]
Guo, Rong [1 ]
Xie, Xinsheng [1 ]
Li, Wei [1 ]
Liu, Delong [1 ]
Song, Yongping [1 ]
Jiang, Zhongxing [1 ]
机构
[1] Zhengzhou Univ, Dept Hematol, Affiliated Hosp 1, Zhengzhou, Henan, Peoples R China
[2] Henan Univ, Joint Natl Lab Antibody Drug Engn, Key Lab Cellular & Mol Immunol Henan Prov, Inst Translat Med,Sch Basic Med, Kaifeng, Henan, Peoples R China
[3] Zhengzhou Univ, Acad Med Sci, Coll Med, Zhengzhou, Henan, Peoples R China
[4] Zhengzhou Univ, Henan Canc Hosp, Affiliated Canc Hosp, Zhengzhou, Henan, Peoples R China
[5] Zhengzhou Univ, Lab Anim Ctr, Sch Med Sci, Zhengzhou, Henan, Peoples R China
基金
中国国家自然科学基金;
关键词
Acute myeloid leukemia; Microenvironment; Single-cell RNA sequencing; Immune phenotypes; Bone marrow; Immune cells; Myeloid cells; T lymphocytes; REGULATORY T-CELLS; BONE-MARROW MICROENVIRONMENT; NATURAL-KILLER-CELLS; DENDRITIC CELL; TH17; CELLS; PERIPHERAL-BLOOD; NK CELLS; EXPRESSION; SUPPRESSION; RELAPSE;
D O I
10.1186/s40364-021-00265-0
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
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页数:16
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