Abstract
Myeloid‐derived suppressor cells (MDSCs) are a heterogeneous cell population that includes immature myeloid cells and the progenitor cells of macrophages, dendritic cells (DCs), monocytes, and neutrophils. The expansion and functional importance of MDSCs in patients with cancer and noncancer pathogenic conditions has been recognized. As a result, there has been growing interest in understanding their roles in acute graft‐versus‐host disease (aGVHD) after allogenetic hematopoietic stem cell transplantation (allo‐HSCT). In order to evaluate possible effects of MDSCs on aGVHD development and clinical outcomes, this study systematically detected the dynamic changes of MDSCs accumulation in patients during the first 100 days after allo‐HSCT, and investigated the levels of other cell types and relative cytokines during MDSCs accumulation. Results showed that accumulation of MDSCs in the graft and in peripheral blood when engraftment might contribute to patients' overall immune suppression and result in the successful control of severe aGVHD and long‐term survival without influence on risk of recurrence after allo‐HSCT. But MDSCs levels in the graft had more favorable predictive abilities. Furthermore, MDSCs proportion significantly increased in patients developing aGVHD after allo‐HSCT. It might be caused by secondary inflammatory response, especially related to high concentrations of IL‐6 and TNF‐α. But this accumulation would not be able to counterbalance the aggravation of aGVHD and would not have influence on clinical outcomes and risk of relapse. Overall, MDSCs might be considered as potential new therapeutic option for aGVHD and achieve long‐term immunological tolerance and survival.
Highlights
Myeloid- derived suppressor cells (MDSCs), originally described in cancer patients, are a heterogeneous cell population that includes immature myeloid cells and the progenitor cells of macrophages, dendritic cells (DCs), monocytes, and neutrophils
MDSCs regulate immunity through several mechanisms that include attenuating the cytotoxicity of natural killer cells (NK), inducing T regulatory cells (Treg), and polarizing immunity toward a tumor-promoting type 2 phenotype through downregulation of interferon-γ(IFN-γ) and upregulation of interleukin-10 (IL-10), etc. [5,6,7,8]
CD14+HLA-DR-/low MDSCs were purified from peripheral blood mononuclear cell (PBMC) of patients
Summary
Myeloid- derived suppressor cells (MDSCs), originally described in cancer patients, are a heterogeneous cell population that includes immature myeloid cells and the progenitor cells of macrophages, dendritic cells (DCs), monocytes, and neutrophils. It has been reported that MDSCs were involved in tumor-associated immunosuppression and played immune regulatory roles in infectious disease, autoimmune disease, trauma, and inflammatory diseases [1,2,3,4]. MDSCs regulate immunity through several mechanisms that include attenuating the cytotoxicity of natural killer cells (NK), inducing T regulatory cells (Treg), and polarizing immunity toward a tumor-promoting type 2 phenotype through downregulation of interferon-γ(IFN-γ) and upregulation of interleukin-10 (IL-10), etc. Values (a) The characteristic of the patients and donors with allo-HSCT. MDSCs regulate immunity through several mechanisms that include attenuating the cytotoxicity of natural killer cells (NK), inducing T regulatory cells (Treg), and polarizing immunity toward a tumor-promoting type 2 phenotype through downregulation of interferon-γ(IFN-γ) and upregulation of interleukin-10 (IL-10), etc. [5,6,7,8].
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