Abnormal proportions and functions of myeloid-derived suppressor cells in peripheral blood of patients with diffuse large B-cell lymphoma

弥漫性大B细胞淋巴瘤患者外周血中髓系来源抑制细胞的比例和功能异常

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Abstract

BACKGROUND: Myeloid-derived suppressor cells (MDSCs) are a subset of immature myeloid cells with immunosuppressive properties. Evidence suggests that abnormal immune system can lead to immune dysfunction and increase the risk of developing diffuse large B-cell lymphoma (DLBCL). This study investigated the abnormality of MDSCs in the peripheral blood of patients with DLBCL. METHODS: Expression, apoptosis, and proliferation of MDSCs was measured in the peripheral blood DLBCL patients and healthy donors (HDs) via flow cytometer. The co-culture groups included the MDSCs and DLBCL cells line and MDSCs and T cells. Using flow cytometry detected MDSCs and T cells proliferation, apoptosis, T cells activation and function in the co-culture groups. RNA transcriptome sequencing analysis was conducted on DLBCL-MDSCs and HDs-MDSCs. Combined with the clinicopathological data of DLBCL patients, the correlation between MDSCs and DLBCL progression was analyzed. RESULTS: The expression of MDSCs in patients newly diagnosed with DLBCL was elevated. DLBCL tumor cells could stimulate MDSCs growth. DLBCL-MDSCs showed stronger immunosuppressive ability to T cells proliferation, activation and secretion of cytokines and associated with several clinical indicators such as Ann Arbor stage, serum LDH level, and lymphoma IPI score. CONCLUSION: This study investigated the abnormality of MDSCs and underscored the critical role of MDSCs in suppressing T cell function in DLBCL patients. It provides certain laboratory evidence for MDSCs as biomarkers of disease progression and treatment response in DLBCL.

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