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Identification of the immunosuppressive effect of γδ T cells correlated to bone morphogenetic protein 2 in acute myeloid leukemia

Description of immune landscapes in malignant microenvironment is critical to the improvement of therapeutic strategies for various tumors. Acute myeloid leukemia (AML) remains a severe life-threatening malignancy and often confronts treatment dilemma in clinic. Although γδ T cells exhibit independe...

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Autores principales: Liang, Shuang, Dong, Tianhui, Yue, Keli, Gao, Haitao, Wu, Ning, Liu, Ruoyang, Chang, Yan, Hao, Le, Hu, Lijuan, Zhao, Ting, Jiang, Qian, Huang, Xiao-Jun, Liu, Jiangying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9618638/
https://www.ncbi.nlm.nih.gov/pubmed/36325350
http://dx.doi.org/10.3389/fimmu.2022.1009709
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author Liang, Shuang
Dong, Tianhui
Yue, Keli
Gao, Haitao
Wu, Ning
Liu, Ruoyang
Chang, Yan
Hao, Le
Hu, Lijuan
Zhao, Ting
Jiang, Qian
Huang, Xiao-Jun
Liu, Jiangying
author_facet Liang, Shuang
Dong, Tianhui
Yue, Keli
Gao, Haitao
Wu, Ning
Liu, Ruoyang
Chang, Yan
Hao, Le
Hu, Lijuan
Zhao, Ting
Jiang, Qian
Huang, Xiao-Jun
Liu, Jiangying
author_sort Liang, Shuang
collection PubMed
description Description of immune landscapes in malignant microenvironment is critical to the improvement of therapeutic strategies for various tumors. Acute myeloid leukemia (AML) remains a severe life-threatening malignancy and often confronts treatment dilemma in clinic. Although γδ T cells exhibit independent and potent cytotoxicity against leukemic cells in vitro and in the mouse models, efficacy of γδ T cell-based immunotherapy on AML patients has seemed unsatisfying so far. How the anti-AML capacity of γδ T cells is suppressed in vivo remains elusive. Herein, we found an aberrant γδ T cells subset expressing CD25(+)CD127(low)Vδ2(+) in the bone marrows of patients with newly diagnosed AML. The emergence of this subset was significantly associated with disease status and risk stratification as well as with the abnormally increased bone morphogenetic protein 2 (BMP2). Mechanistically, BMP2 could directly induce CD25(+)CD127(low)Vδ2(+) γδ T cells (named as Reg-Vδ2) in vitro. The immunosuppressive features of Reg-Vδ2 cells were identified by combining immunophenotypical and functional data. Furthermore, inhibition of BMP2 pathway significantly blocked the emergence of Reg-Vδ2 cells and enhanced the anti-AML immunity in humanized mice. These findings not only provide a novel insight into the mechanisms of immunosuppression in the context of leukemia, but also suggest potential targets for the treatment of AML and other hematopoietic malignancies.
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spelling pubmed-96186382022-11-01 Identification of the immunosuppressive effect of γδ T cells correlated to bone morphogenetic protein 2 in acute myeloid leukemia Liang, Shuang Dong, Tianhui Yue, Keli Gao, Haitao Wu, Ning Liu, Ruoyang Chang, Yan Hao, Le Hu, Lijuan Zhao, Ting Jiang, Qian Huang, Xiao-Jun Liu, Jiangying Front Immunol Immunology Description of immune landscapes in malignant microenvironment is critical to the improvement of therapeutic strategies for various tumors. Acute myeloid leukemia (AML) remains a severe life-threatening malignancy and often confronts treatment dilemma in clinic. Although γδ T cells exhibit independent and potent cytotoxicity against leukemic cells in vitro and in the mouse models, efficacy of γδ T cell-based immunotherapy on AML patients has seemed unsatisfying so far. How the anti-AML capacity of γδ T cells is suppressed in vivo remains elusive. Herein, we found an aberrant γδ T cells subset expressing CD25(+)CD127(low)Vδ2(+) in the bone marrows of patients with newly diagnosed AML. The emergence of this subset was significantly associated with disease status and risk stratification as well as with the abnormally increased bone morphogenetic protein 2 (BMP2). Mechanistically, BMP2 could directly induce CD25(+)CD127(low)Vδ2(+) γδ T cells (named as Reg-Vδ2) in vitro. The immunosuppressive features of Reg-Vδ2 cells were identified by combining immunophenotypical and functional data. Furthermore, inhibition of BMP2 pathway significantly blocked the emergence of Reg-Vδ2 cells and enhanced the anti-AML immunity in humanized mice. These findings not only provide a novel insight into the mechanisms of immunosuppression in the context of leukemia, but also suggest potential targets for the treatment of AML and other hematopoietic malignancies. Frontiers Media S.A. 2022-10-17 /pmc/articles/PMC9618638/ /pubmed/36325350 http://dx.doi.org/10.3389/fimmu.2022.1009709 Text en Copyright © 2022 Liang, Dong, Yue, Gao, Wu, Liu, Chang, Hao, Hu, Zhao, Jiang, Huang and Liu https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Liang, Shuang
Dong, Tianhui
Yue, Keli
Gao, Haitao
Wu, Ning
Liu, Ruoyang
Chang, Yan
Hao, Le
Hu, Lijuan
Zhao, Ting
Jiang, Qian
Huang, Xiao-Jun
Liu, Jiangying
Identification of the immunosuppressive effect of γδ T cells correlated to bone morphogenetic protein 2 in acute myeloid leukemia
title Identification of the immunosuppressive effect of γδ T cells correlated to bone morphogenetic protein 2 in acute myeloid leukemia
title_full Identification of the immunosuppressive effect of γδ T cells correlated to bone morphogenetic protein 2 in acute myeloid leukemia
title_fullStr Identification of the immunosuppressive effect of γδ T cells correlated to bone morphogenetic protein 2 in acute myeloid leukemia
title_full_unstemmed Identification of the immunosuppressive effect of γδ T cells correlated to bone morphogenetic protein 2 in acute myeloid leukemia
title_short Identification of the immunosuppressive effect of γδ T cells correlated to bone morphogenetic protein 2 in acute myeloid leukemia
title_sort identification of the immunosuppressive effect of γδ t cells correlated to bone morphogenetic protein 2 in acute myeloid leukemia
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9618638/
https://www.ncbi.nlm.nih.gov/pubmed/36325350
http://dx.doi.org/10.3389/fimmu.2022.1009709
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