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


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.

SUBMITTER: Hyun SY 

PROVIDER: S-EPMC7541151 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Immunosuppressive role of CD11b<sup>+</sup> CD33<sup>+</sup> HLA-DR<sup>-</sup> myeloid-derived suppressor cells-like blast subpopulation in acute myeloid leukemia.

Hyun Shin Young SY   Na Eun Jung EJ   Jang Ji Eun JE   Chung Haerim H   Kim Soo Jeong SJ   Kim Jin Seok JS   Kong Jee Hyun JH   Shim Kwang Yong KY   Lee Jong In JI   Min Yoo Hong YH   Cheong June-Won JW  

Cancer medicine 20200811 19


<h4>Objective</h4>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.<h4>Methods</h4>CD11b<sup>+</sup> CD33<sup>+</sup> HLA-DR<sup>-</sup> MDSC-like blasts from bone marrow mononuclear cells of patients with AML were analyzed. To investigate their T cell-suppre  ...[more]

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