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

被引:66
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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共 106 条
  • [1] Prognostic value of Th17 cells in acute leukemia
    Abousamra, Nashwa Khairat
    El-Din, Manal Salah
    Helal, Randah
    [J]. MEDICAL ONCOLOGY, 2013, 30 (04)
  • [2] PDGF upregulates CLEC-2 to induce T regulatory cells
    Agrawal, Sudhanshu
    Ganguly, Sreerupa
    Hajian, Pega
    Cao, Jia-Ning
    Agrawal, Anshu
    [J]. ONCOTARGET, 2015, 6 (30) : 28621 - 28632
  • [3] Dynamic changes in glioma macrophage populations after radiotherapy reveal CSF-1R inhibition as a strategy to overcome resistance
    Akkari, Leila
    Bowman, Robert L.
    Tessier, Jeremy
    Klemm, Florian
    Handgraaf, Shanna M.
    de Groot, Marnix
    Quail, Daniela F.
    Tillard, Lucie
    Gadiot, Jules
    Huse, Jason T.
    Brandsma, Dieta
    Westerga, Johan
    Watts, Colin
    Joyce, Johanna A.
    [J]. SCIENCE TRANSLATIONAL MEDICINE, 2020, 12 (552)
  • [4] Acute myeloid leukemia cells polarize macrophages towards a leukemia supporting state in a Growth factor independence 1 dependent manner
    Al-Matary, Yahya S.
    Botezatu, Lacramioara
    Opalka, Bertram
    Hoenes, Judith M.
    Lams, Robert F.
    Thivakaran, Aniththa
    Schuette, Judith
    Koester, Renata
    Lennartz, Klaus
    Schroeder, Thomas
    Haas, Rainer
    Duehrsen, Ulrich
    Khandanpour, Cyrus
    [J]. HAEMATOLOGICA, 2016, 101 (10) : 1216 - 1227
  • [5] Defining the emergence of myeloid-derived suppressor cells in breast cancer using single-cell transcriptomics
    Alshetaiwi, Hamad
    Pervolarakis, Nicholas
    McIntyre, Laura Lynn
    Ma, Dennis
    Quy Nguyen
    Rath, Jan Akara
    Nee, Kevin
    Hernandez, Grace
    Evans, Katrina
    Torosian, Leona
    Silva, Anushka
    Walsh, Craig
    Kessenbrock, Kai
    [J]. SCIENCE IMMUNOLOGY, 2020, 5 (44)
  • [6] Dendritic cell vaccination as postremission treatment to prevent or delay relapse in acute myeloid leukemia
    Anguille, Sebastien
    Van de Velde, Ann L.
    Smits, Evelien L.
    Van Tendeloo, Viggo F.
    Juliusson, Gunnar
    Cools, Nathalie
    Nijs, Griet
    Stein, Barbara
    Lion, Eva
    Van Driessche, Ann
    Vandenbosch, Irma
    Verlinden, Anke
    Gadisseur, Alain P.
    Schroyens, Wilfried A.
    Muylle, Ludo
    Vermeulen, Katrien
    Maes, Marie-Berthe
    Deiteren, Kathleen
    Malfait, Ronald
    Gostick, Emma
    Lammens, Martin
    Couttenye, Marie M.
    Jorens, Philippe
    Goossens, Herman
    Price, David A.
    Ladell, Kristin
    Oka, Yoshihiro
    Fujiki, Fumihiro
    Oji, Yusuke
    Sugiyama, Haruo
    Berneman, Zwi N.
    [J]. BLOOD, 2017, 130 (15) : 1713 - 1721
  • [7] Predictive biomarkers for cancer immunotherapy with immune checkpoint inhibitors
    Bai, Rilan
    Lv, Zheng
    Xu, Dongsheng
    Cui, Jiuwei
    [J]. BIOMARKER RESEARCH, 2020, 8 (01)
  • [8] Activating and inhibitory IgG Fc receptors on human DCs mediate opposing functions
    Boruchov, AM
    Heller, G
    Veri, MC
    Bonvini, E
    Ravetch, JV
    Young, JW
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 2005, 115 (10) : 2914 - 2923
  • [9] Acute myeloid leukaemia disrupts endogenous myelo-erythropoiesis by compromising the adipocyte bone marrow niche
    Boyd, Allison L.
    Reid, Jennifer C.
    Salci, Kyle R.
    Aslostovar, Lili
    Benoit, Yannick D.
    Shapovalova, Zoya
    Nakanishi, Mio
    Porras, Deanna P.
    Almakadi, Mohammed
    Campbell, Clinton J. V.
    Jackson, Michael F.
    Ross, Catherine A.
    Foley, Ronan
    Leber, Brian
    Allan, David S.
    Sabloff, Mitchell
    Xenocostas, Anargyros
    Collins, Tony J.
    Bhatia, Mickie
    [J]. NATURE CELL BIOLOGY, 2017, 19 (11) : 1336 - +
  • [10] Circulating T cell-monocyte complexes are markers of immune perturbations
    Burel, Julie G.
    Pomaznoy, Mikhail
    Arlehamn, Cecilia S. Lindestam
    Weiskopf, Daniela
    Antunes, Ricardo da Silva
    Jung, Yunmin
    Babor, Mariana
    Schulten, Veronique
    Seumois, Gregory
    Greenbaum, Jason A.
    Premawansa, Sunil
    Premawansa, Gayani
    Wijewickrama, Ananda
    Vidanagama, Dhammika
    Gunasena, Bandu
    Tippalagama, Rashmi
    DeSilva, Aruna D.
    Gilman, Robert H.
    Saito, Mayuko
    Taplitz, Randy
    Ley, Klaus
    Vijayanand, Pandurangan
    Sette, Alessandro
    Peters, Bjoern
    [J]. ELIFE, 2019, 8