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Matrix Metalloproteinase-9 in Monocytic Myeloid-Derived Suppressor Cells Correlate with Early Infections and Clinical Outcomes in Allogeneic Hematopoietic Stem Cell Transplantation.
Biol Blood Marrow Transplant. 2018 01; 24(1):32-42.BB

Abstract

The recovery of myeloid-derived suppressor cells (MDSCs) and its relevance in clinical acute graft-versus-host disease (GVHD) and post-hematopoietic stem cell transplantation (HSCT) infections remain to be fully characterized. We examined the expansion of circulating monocytic (M-) MDSCs and granulocytic (G-) MDSCs at the time of engraftment in 130 patients undergoing allogeneic HSCT (allo-HSCT). Compared with the G-MDSC group, the high M-MDSC group had a higher infection rate within 100 days, along with worse 1-year cumulative incidence of treatment-related mortality (TRM) and 2-year probability of event-free survival (EFS). The frequency of M-MDSCs was associated with preceding severe mucositis. Transcriptome profiling analysis of 2 isolated MDSC subtype showed significantly greater matrix metalloproteinase-9 (MMP-9) expression in M-MDSCs than in G-MDSCs. M-MDSCs produced abundantly more MMP-9. Importantly, compared with G-MDSCs, M-MDSCs isolated from patients post-HSCT had a greater capacity to suppress T cell responses, and MMP-9 blockade more forcefully inhibited their immunosuppressive effect. MMP-9 levels also were associated with the occurrence of infections and with transplantation outcomes. Based on these findings, we identify M-MDSCs as a major contributor to infections early after allo-HSCT and worse clinical outcomes via MMP-9.

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Lee SE
Department of Hematology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea.
Lim JY
Department of Hematology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea.
Kim TW
Department of Hematology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea.
Jeon YW
Department of Hematology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea.
Yoon JH
Department of Hematology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea.
Cho BS
Department of Hematology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea; Leukemia Research Institute, The Catholic University of Korea, Seoul, Republic of Korea.
Eom KS
Department of Hematology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea; Leukemia Research Institute, The Catholic University of Korea, Seoul, Republic of Korea.
Kim YJ
Department of Hematology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea; Leukemia Research Institute, The Catholic University of Korea, Seoul, Republic of Korea.
Kim HJ
Department of Hematology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea; Leukemia Research Institute, The Catholic University of Korea, Seoul, Republic of Korea.
Lee S
Department of Hematology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea; Leukemia Research Institute, The Catholic University of Korea, Seoul, Republic of Korea.
Cho SG
Department of Hematology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea.
Kim DW
Department of Hematology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea; Leukemia Research Institute, The Catholic University of Korea, Seoul, Republic of Korea.
Lee JW
Department of Hematology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea.
Min WS
Department of Hematology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea.
Shin DM
College of Human Ecology, Seoul National University, Seoul, Republic of Korea.
Choi EY
Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.
Min CK
Department of Hematology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea; Leukemia Research Institute, The Catholic University of Korea, Seoul, Republic of Korea. Electronic address: ckmin@catholic.ac.kr.

MeSH

AdultFemaleGene Expression ProfilingGraft vs Host DiseaseGranulocytesHematopoietic Stem Cell TransplantationHumansInfectionsMaleMatrix Metalloproteinase 9Middle AgedMonocytesMyeloid-Derived Suppressor CellsTransplantation, HomologousTreatment Outcome

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28844945

Citation

Lee, Sung-Eun, et al. "Matrix Metalloproteinase-9 in Monocytic Myeloid-Derived Suppressor Cells Correlate With Early Infections and Clinical Outcomes in Allogeneic Hematopoietic Stem Cell Transplantation." Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, vol. 24, no. 1, 2018, pp. 32-42.
Lee SE, Lim JY, Kim TW, et al. Matrix Metalloproteinase-9 in Monocytic Myeloid-Derived Suppressor Cells Correlate with Early Infections and Clinical Outcomes in Allogeneic Hematopoietic Stem Cell Transplantation. Biol Blood Marrow Transplant. 2018;24(1):32-42.
Lee, S. E., Lim, J. Y., Kim, T. W., Jeon, Y. W., Yoon, J. H., Cho, B. S., Eom, K. S., Kim, Y. J., Kim, H. J., Lee, S., Cho, S. G., Kim, D. W., Lee, J. W., Min, W. S., Shin, D. M., Choi, E. Y., & Min, C. K. (2018). Matrix Metalloproteinase-9 in Monocytic Myeloid-Derived Suppressor Cells Correlate with Early Infections and Clinical Outcomes in Allogeneic Hematopoietic Stem Cell Transplantation. Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, 24(1), 32-42. https://doi.org/10.1016/j.bbmt.2017.08.017
Lee SE, et al. Matrix Metalloproteinase-9 in Monocytic Myeloid-Derived Suppressor Cells Correlate With Early Infections and Clinical Outcomes in Allogeneic Hematopoietic Stem Cell Transplantation. Biol Blood Marrow Transplant. 2018;24(1):32-42. PubMed PMID: 28844945.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Matrix Metalloproteinase-9 in Monocytic Myeloid-Derived Suppressor Cells Correlate with Early Infections and Clinical Outcomes in Allogeneic Hematopoietic Stem Cell Transplantation. AU - Lee,Sung-Eun, AU - Lim,Ji-Young, AU - Kim,Tae Woo, AU - Jeon,Young-Woo, AU - Yoon,Jae-Ho, AU - Cho,Byung-Sik, AU - Eom,Ki-Seong, AU - Kim,Yoo-Jin, AU - Kim,Hee-Je, AU - Lee,Seok, AU - Cho,Seok-Goo, AU - Kim,Dong-Wook, AU - Lee,Jong Wook, AU - Min,Woo-Sung, AU - Shin,Dong-Mi, AU - Choi,Eun Young, AU - Min,Chang-Ki, Y1 - 2017/08/24/ PY - 2017/07/03/received PY - 2017/08/12/accepted PY - 2017/8/29/pubmed PY - 2019/3/9/medline PY - 2017/8/29/entrez KW - Allogeneic hematopoietic stem cell transplantation KW - Infection KW - Matrix metalloproteinase-9 KW - Myeloid-derived suppressor cell KW - Treatment-related mortality SP - 32 EP - 42 JF - Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation JO - Biol. Blood Marrow Transplant. VL - 24 IS - 1 N2 - The recovery of myeloid-derived suppressor cells (MDSCs) and its relevance in clinical acute graft-versus-host disease (GVHD) and post-hematopoietic stem cell transplantation (HSCT) infections remain to be fully characterized. We examined the expansion of circulating monocytic (M-) MDSCs and granulocytic (G-) MDSCs at the time of engraftment in 130 patients undergoing allogeneic HSCT (allo-HSCT). Compared with the G-MDSC group, the high M-MDSC group had a higher infection rate within 100 days, along with worse 1-year cumulative incidence of treatment-related mortality (TRM) and 2-year probability of event-free survival (EFS). The frequency of M-MDSCs was associated with preceding severe mucositis. Transcriptome profiling analysis of 2 isolated MDSC subtype showed significantly greater matrix metalloproteinase-9 (MMP-9) expression in M-MDSCs than in G-MDSCs. M-MDSCs produced abundantly more MMP-9. Importantly, compared with G-MDSCs, M-MDSCs isolated from patients post-HSCT had a greater capacity to suppress T cell responses, and MMP-9 blockade more forcefully inhibited their immunosuppressive effect. MMP-9 levels also were associated with the occurrence of infections and with transplantation outcomes. Based on these findings, we identify M-MDSCs as a major contributor to infections early after allo-HSCT and worse clinical outcomes via MMP-9. SN - 1523-6536 UR - https://www.unboundmedicine.com/medline/citation/28844945/Matrix_Metalloproteinase_9_in_Monocytic_Myeloid_Derived_Suppressor_Cells_Correlate_with_Early_Infections_and_Clinical_Outcomes_in_Allogeneic_Hematopoietic_Stem_Cell_Transplantation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1083-8791(17)30652-3 DB - PRIME DP - Unbound Medicine ER -
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