Immunosuppressive role of CD11b+CD33+HLA‐DR− myeloid‐derived suppressor cells‐like blast subpopulation in acute myeloid leukemia
| Autor: | Ji Eun Jang, Kwang Yong Shim, Soo Jeong Kim, Haerim Chung, Jin Seok Kim, Jong In Lee, Eun Jung Na, Jee Hyun Kong, June-Won Cheong, Shin Young Hyun, Yoo Hong Min |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cancer Research T cell medicine.medical_treatment CD33 Hematopoietic stem cell transplantation acute myeloid leukemia lcsh:RC254-282 03 medical and health sciences 0302 clinical medicine hemic and lymphatic diseases medicine Cytotoxic T cell Radiology Nuclear Medicine and imaging myeloid‐derived suppressor cells business.industry arginase inducible nitric oxide synthase Myeloid leukemia lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens 030104 developmental biology medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Cancer research Myeloid-derived Suppressor Cell Bone marrow prognosis business CD8 |
| Zdroj: | Cancer Medicine, Vol 9, Iss 19, Pp 7007-7017 (2020) |
| ISSN: | 2045-7634 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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