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Immunosuppressive role of CD11b + CD33 + HLA-DR - myeloid-derived suppressor cells-like blast subpopulation in acute myeloid leukemia

Authors
 Shin Young Hyun  ;  Eun Jung Na  ;  Ji Eun Jang  ;  Haerim Chung  ;  Soo Jeong Kim  ;  Jin Seok Kim  ;  Jee Hyun Kong  ;  Kwang Yong Shim  ;  Jong In Lee  ;  Yoo Hong Min  ;  June-Won Cheong 
Citation
 CANCER MEDICINE, Vol.9(19) : 7007-7017, 2020-10 
Journal Title
 CANCER MEDICINE 
Issue Date
2020-10
Keywords
acute myeloid leukemia ; arginase ; inducible nitric oxide synthase ; myeloid-derived suppressor cells ; prognosis
Abstract
Objective: Myeloid-derived suppressor cells (MDSCs) facilitate tumor growth and development by suppressing T cell function; however, their role in acute myeloid leukemia (AML) remains unclear. Here, we investigated the immunosuppressive role and prognostic value of blasts with an MDSC-like phenotype. Methods: CD11b+ CD33+ HLA-DR- MDSC-like blasts from bone marrow mononuclear cells of patients with AML were analyzed. To investigate their T cell-suppressing function, MDSC-like blasts were isolated using flow cytometry and co-cultured with CD8+ cytotoxic T cells and NB4 leukemic cells. Treatment outcomes were then compared between the MDSC-like blasts low (≤9.76%) and high (>9.76%) groups to identify clinical significance. Results: MDSC-like blasts showed higher expression of arginase-1 and inducible nitric oxide synthase. Isolated MDSC-like blasts significantly suppressed CD8+ T cell proliferation induced by phytohemagglutinin A. NB4 cell proliferation was significantly suppressed upon co-culture with CD8+ cytotoxic T cells and partially restored upon co-culture with MDSC-like blasts. Patients with high MDSC-like blasts at diagnosis showed substantially shorter overall survival and leukemia-free survival relative to low MDSC-like blasts patients, with subgroup analysis showing statistically significant differences in patients not receiving allogeneic hematopoietic stem cell transplantation. Conclusion: We demonstrated that MDSC-like blasts drive AML-specific immune-escape mechanisms by suppressing T cell proliferation and restoring T cell-suppressed NB4 cell proliferation, with clinically higher fractions of MDSC-like blasts at diagnosis resulting in poor prognosis.
Files in This Item:
T202004119.pdf Download
DOI
10.1002/cam4.3360
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Soo Jeong(김수정) ORCID logo https://orcid.org/0000-0001-8859-3573
Kim, Jin Seok(김진석) ORCID logo https://orcid.org/0000-0001-8986-8436
Min, Yoo Hong(민유홍) ORCID logo https://orcid.org/0000-0001-8542-9583
Jang, Ji Eun(장지은) ORCID logo https://orcid.org/0000-0001-8832-1412
Cheong, June-Won(정준원) ORCID logo https://orcid.org/0000-0002-1744-0921
Chung, Hae Rim(정해림) ORCID logo https://orcid.org/0000-0002-7926-9285
Hyun, Shin Yong(현신영) ORCID logo https://orcid.org/0000-0002-8137-8675
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/180128
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