Monocytes from patients with myelodysplastic syndrome inhibit natural killer cell-mediated antitumor function through the CD200/CD200R pathway

IF 4.7 2区医学 Q2 IMMUNOLOGY International immunopharmacology Pub Date : 2025-03-05 DOI:10.1016/j.intimp.2025.114394

Yixuan Guo , Zhaoyun Liu , Mengyue Tian , Xiaohan Liu , Nianbin Li , Kai Ding , Hui Liu , Rong Fu

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Abstract

Background

Reports on the expression of CD200 in monocytes are scarce, and the role of monocytes in patients with myelodysplastic syndrome (MDS) remains unclear. Additionally, monocytes have been implicated in suppressing NK cell function. Therefore, this study aimed to explore the possible mechanism by which monocytes regulate NK cell function through CD200 in patients with MDS.

Methods

We collected samples from patients with MDS, those with acute myeloid leukemia, and healthy controls. We detected the expression of CD200 on the surface of monocytes and its receptor CD200R on the surface of NK cells using flow cytometry, explored the effect of the CD200/CD200R pathway on activating STAT3 and ERK of NK cells, and studied the effect of blocking CD200/CD200R pathway on NK cells.

Results

The expression of CD200 on the surface of monocytes and CD200R on the surface of NK cells in patients with MDS was higher than those in healthy controls. After adding CD200 monoclonal antibody to the co-culture system of monocytes and NK cells, the expression of activated receptors CD107a, CD226, and NKG2D on NK cells significantly increased. We then used siRNA to silence CD200R expression in NK-92 cells and found that the blockade of CD200R enhanced the phosphorylation levels of ERK and STAT3.

Conclusions

Our study found that elevated CD200 expression on monocytes in patients with MDS correlates with poor prognosis, suggesting CD200 as a potential prognostic marker. Blocking CD200 enhances NK cell activation and cytotoxicity, indicating that CD200 blockade therapy could enhance antitumor responses in patients with MDS.

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骨髓增生异常综合征患者的单核细胞通过CD200/CD200R途径抑制自然杀伤细胞介导的抗肿瘤功能

关于CD200在单核细胞中的表达的报道很少，单核细胞在骨髓增生异常综合征（MDS）患者中的作用尚不清楚。此外，单核细胞还参与抑制NK细胞功能。因此，本研究旨在探讨单核细胞通过CD200调节MDS患者NK细胞功能的可能机制。方法收集MDS患者、急性髓系白血病患者和健康对照者的样本。我们利用流式细胞术检测单核细胞表面CD200及其受体CD200R在NK细胞表面的表达，探讨CD200/CD200R通路对NK细胞STAT3和ERK激活的影响，并研究阻断CD200/CD200R通路对NK细胞的影响。结果MDS患者单核细胞表面CD200和NK细胞表面CD200R的表达均高于正常对照组。在单核细胞与NK细胞共培养体系中加入CD200单克隆抗体后，活化受体CD107a、CD226和NKG2D在NK细胞上的表达显著增加。然后我们使用siRNA沉默NK-92细胞中CD200R的表达，发现CD200R的阻断增强了ERK和STAT3的磷酸化水平。结论我们的研究发现MDS患者单核细胞CD200表达升高与预后不良相关，提示CD200可能是一个潜在的预后标志物。阻断CD200可增强NK细胞活化和细胞毒性，表明CD200阻断治疗可增强MDS患者的抗肿瘤反应。

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Penicillin and streptomycin

来源期刊

International immunopharmacology 医学-免疫学

CiteScore

8.40

自引率

3.60%

发文量

935

审稿时长

53 days

期刊介绍： International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome. The subject material appropriate for submission includes: • Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders. • Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state. • Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses. • Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action. • Agents that activate genes or modify transcription and translation within the immune response. • Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active. • Production, function and regulation of cytokines and their receptors. • Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.