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

IF 4.8 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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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.