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

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.

CD200R; ERK; MDS; Monocytes; NK cells.