Bisecting GlcNAc expression by bone marrow stromal cells modulates TGF-β1-driven macrophage polarization in myeloid leukemias
Accumulating evidence have highlighted the critical role of tumor-associated macrophages (TAMs) in promoting immune evasion and disease progression in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Combined single-cell RNA sequencing, flow cytometry, and immunohistochemistry stud...
Saved in:
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Ferrata Storti Foundation
2025-05-01
|
| Series: | Haematologica |
| Online Access: | https://haematologica.org/article/view/12071 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849328470632431616 |
|---|---|
| author | Jingjing Feng Junjie Gou Yi Wang Wei Wei Yihan Ma Xueting Ren Chongfu Zhao Xiaoliang Cheng Lei Lei Zengqi Tan Feng Guan Xiang Li |
| author_facet | Jingjing Feng Junjie Gou Yi Wang Wei Wei Yihan Ma Xueting Ren Chongfu Zhao Xiaoliang Cheng Lei Lei Zengqi Tan Feng Guan Xiang Li |
| author_sort | Jingjing Feng |
| collection | DOAJ |
| description |
Accumulating evidence have highlighted the critical role of tumor-associated macrophages (TAMs) in promoting immune evasion and disease progression in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Combined single-cell RNA sequencing, flow cytometry, and immunohistochemistry studies of the innate immune compartment in bone marrow of MDS/AML reveal a shift toward a tumor-supportive M2-polarized macrophage as well as the expression of programmed cell death-ligand 1 (PD-L1) in this cell lineage. We found the leukemic stroma cells with high level of TGFβ1 secretion can determine TAMs toward M2-polarized subtype. Further mechanistic investigations revealed that bone marrow stromal cells with specific glycans, reduced bisecting N-acetylglucosamine (GlcNAc) levels, in MDS/AML promoted M2-polarized subtype through the secretion of TGFβ1, which elevated PD-L1 expression and thereby impaired CD8+ T cell function. Our study provides insights into the mechanisms of selectively modifying specific glycans in bone marrow stroma cells may contribute to targeting strategies aimed at the tumor microenvironment.
|
| format | Article |
| id | doaj-art-dc3cec4b08e04a78b6c968cb43672518 |
| institution | Kabale University |
| issn | 0390-6078 1592-8721 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Ferrata Storti Foundation |
| record_format | Article |
| series | Haematologica |
| spelling | doaj-art-dc3cec4b08e04a78b6c968cb436725182025-08-20T03:47:36ZengFerrata Storti FoundationHaematologica0390-60781592-87212025-05-01999110.3324/haematol.2024.287091Bisecting GlcNAc expression by bone marrow stromal cells modulates TGF-β1-driven macrophage polarization in myeloid leukemiasJingjing Feng0Junjie Gou1Yi Wang2Wei Wei3Yihan Ma4Xueting Ren5Chongfu Zhao6Xiaoliang Cheng7Lei Lei8Zengqi Tan9Feng Guan10Xiang Li11Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest University, Xi’an, ShaanxiKey Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest University, Xi’an, ShaanxiDepartment of Hematology, Provincial People’s Hospital, Xi’an, ShaanxiKey Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest University, Xi’an, ShaanxiKey Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest University, Xi’an, ShaanxiDepartment of Oncology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, ShaanxiKey Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest University, Xi’an, ShaanxiNorthwest University Qlife Precision Medicine Center, Xi’an, ShaanxiKey Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest University, Xi’an, ShaanxiKey Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest University, Xi’an, Shaanxi, China; Institute of Hematology, School of Medicine, Northwest University, Xi’an, ShaanxiKey Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest University, Xi’an, ShaanxiKey Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest University, Xi’an, Shaanxi, China; Institute of Hematology, School of Medicine, Northwest University, Xi’an, Shaanxi Accumulating evidence have highlighted the critical role of tumor-associated macrophages (TAMs) in promoting immune evasion and disease progression in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Combined single-cell RNA sequencing, flow cytometry, and immunohistochemistry studies of the innate immune compartment in bone marrow of MDS/AML reveal a shift toward a tumor-supportive M2-polarized macrophage as well as the expression of programmed cell death-ligand 1 (PD-L1) in this cell lineage. We found the leukemic stroma cells with high level of TGFβ1 secretion can determine TAMs toward M2-polarized subtype. Further mechanistic investigations revealed that bone marrow stromal cells with specific glycans, reduced bisecting N-acetylglucosamine (GlcNAc) levels, in MDS/AML promoted M2-polarized subtype through the secretion of TGFβ1, which elevated PD-L1 expression and thereby impaired CD8+ T cell function. Our study provides insights into the mechanisms of selectively modifying specific glycans in bone marrow stroma cells may contribute to targeting strategies aimed at the tumor microenvironment. https://haematologica.org/article/view/12071 |
| spellingShingle | Jingjing Feng Junjie Gou Yi Wang Wei Wei Yihan Ma Xueting Ren Chongfu Zhao Xiaoliang Cheng Lei Lei Zengqi Tan Feng Guan Xiang Li Bisecting GlcNAc expression by bone marrow stromal cells modulates TGF-β1-driven macrophage polarization in myeloid leukemias Haematologica |
| title | Bisecting GlcNAc expression by bone marrow stromal cells modulates TGF-β1-driven macrophage polarization in myeloid leukemias |
| title_full | Bisecting GlcNAc expression by bone marrow stromal cells modulates TGF-β1-driven macrophage polarization in myeloid leukemias |
| title_fullStr | Bisecting GlcNAc expression by bone marrow stromal cells modulates TGF-β1-driven macrophage polarization in myeloid leukemias |
| title_full_unstemmed | Bisecting GlcNAc expression by bone marrow stromal cells modulates TGF-β1-driven macrophage polarization in myeloid leukemias |
| title_short | Bisecting GlcNAc expression by bone marrow stromal cells modulates TGF-β1-driven macrophage polarization in myeloid leukemias |
| title_sort | bisecting glcnac expression by bone marrow stromal cells modulates tgf β1 driven macrophage polarization in myeloid leukemias |
| url | https://haematologica.org/article/view/12071 |
| work_keys_str_mv | AT jingjingfeng bisectingglcnacexpressionbybonemarrowstromalcellsmodulatestgfb1drivenmacrophagepolarizationinmyeloidleukemias AT junjiegou bisectingglcnacexpressionbybonemarrowstromalcellsmodulatestgfb1drivenmacrophagepolarizationinmyeloidleukemias AT yiwang bisectingglcnacexpressionbybonemarrowstromalcellsmodulatestgfb1drivenmacrophagepolarizationinmyeloidleukemias AT weiwei bisectingglcnacexpressionbybonemarrowstromalcellsmodulatestgfb1drivenmacrophagepolarizationinmyeloidleukemias AT yihanma bisectingglcnacexpressionbybonemarrowstromalcellsmodulatestgfb1drivenmacrophagepolarizationinmyeloidleukemias AT xuetingren bisectingglcnacexpressionbybonemarrowstromalcellsmodulatestgfb1drivenmacrophagepolarizationinmyeloidleukemias AT chongfuzhao bisectingglcnacexpressionbybonemarrowstromalcellsmodulatestgfb1drivenmacrophagepolarizationinmyeloidleukemias AT xiaoliangcheng bisectingglcnacexpressionbybonemarrowstromalcellsmodulatestgfb1drivenmacrophagepolarizationinmyeloidleukemias AT leilei bisectingglcnacexpressionbybonemarrowstromalcellsmodulatestgfb1drivenmacrophagepolarizationinmyeloidleukemias AT zengqitan bisectingglcnacexpressionbybonemarrowstromalcellsmodulatestgfb1drivenmacrophagepolarizationinmyeloidleukemias AT fengguan bisectingglcnacexpressionbybonemarrowstromalcellsmodulatestgfb1drivenmacrophagepolarizationinmyeloidleukemias AT xiangli bisectingglcnacexpressionbybonemarrowstromalcellsmodulatestgfb1drivenmacrophagepolarizationinmyeloidleukemias |