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 p...
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| Format: | Article |
| Language: | English |
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Wiley
2020-10-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.3360 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Shin Young Hyun |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-a2cc1e74ec39473298bc2fa62e1250c2 |
| institution | Kabale University |
| issn | 2045-7634 |
| language | English |
| publishDate | 2020-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj-art-a2cc1e74ec39473298bc2fa62e1250c22024-12-11T08:05:11ZengWileyCancer Medicine2045-76342020-10-019197007701710.1002/cam4.3360Immunosuppressive role of CD11b+CD33+HLA‐DR− myeloid‐derived suppressor cells‐like blast subpopulation in acute myeloid leukemiaShin Young Hyun0Eun Jung Na1Ji Eun Jang2Haerim Chung3Soo Jeong Kim4Jin Seok Kim5Jee Hyun Kong6Kwang Yong Shim7Jong In Lee8Yoo Hong Min9June‐Won Cheong10Department of Internal Medicine Yonsei University Wonju College of Medicine Kangwon‐do South KoreaDepartment of Internal Medicine Yonsei University Wonju College of Medicine Kangwon‐do South KoreaAvison Biomedical Research Center Yonsei University College of Medicine Seoul South KoreaDepartment of Internal Medicine Yonsei University College of Medicine Seoul South KoreaDepartment of Internal Medicine Yonsei University College of Medicine Seoul South KoreaDepartment of Internal Medicine Yonsei University College of Medicine Seoul South KoreaDepartment of Internal Medicine Yonsei University Wonju College of Medicine Kangwon‐do South KoreaDepartment of Internal Medicine Yonsei University Wonju College of Medicine Kangwon‐do South KoreaDepartment of Internal Medicine Yonsei University Wonju College of Medicine Kangwon‐do South KoreaAvison Biomedical Research Center Yonsei University College of Medicine Seoul South KoreaAvison Biomedical Research Center Yonsei University College of Medicine Seoul South KoreaAbstract 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.https://doi.org/10.1002/cam4.3360acute myeloid leukemiaarginaseinducible nitric oxide synthasemyeloid‐derived suppressor cellsprognosis |
| spellingShingle | 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 Immunosuppressive role of CD11b+CD33+HLA‐DR− myeloid‐derived suppressor cells‐like blast subpopulation in acute myeloid leukemia Cancer Medicine acute myeloid leukemia arginase inducible nitric oxide synthase myeloid‐derived suppressor cells prognosis |
| title | Immunosuppressive role of CD11b+CD33+HLA‐DR− myeloid‐derived suppressor cells‐like blast subpopulation in acute myeloid leukemia |
| title_full | Immunosuppressive role of CD11b+CD33+HLA‐DR− myeloid‐derived suppressor cells‐like blast subpopulation in acute myeloid leukemia |
| title_fullStr | Immunosuppressive role of CD11b+CD33+HLA‐DR− myeloid‐derived suppressor cells‐like blast subpopulation in acute myeloid leukemia |
| title_full_unstemmed | Immunosuppressive role of CD11b+CD33+HLA‐DR− myeloid‐derived suppressor cells‐like blast subpopulation in acute myeloid leukemia |
| title_short | Immunosuppressive role of CD11b+CD33+HLA‐DR− myeloid‐derived suppressor cells‐like blast subpopulation in acute myeloid leukemia |
| title_sort | immunosuppressive role of cd11b cd33 hla dr myeloid derived suppressor cells like blast subpopulation in acute myeloid leukemia |
| topic | acute myeloid leukemia arginase inducible nitric oxide synthase myeloid‐derived suppressor cells prognosis |
| url | https://doi.org/10.1002/cam4.3360 |
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