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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...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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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. |
format | Online Article Text |
id | pubmed-9618638 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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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