Bone marrow CD14+CD206+ M2-like monocyte-macrophages as a potential complementary biomarker for bone marrow MRD in high-risk neuroblastoma

Neuroblastoma (NB) is a highly aggressive pediatric malignancy, frequently associated with a substantial risk of bone marrow metastasis and recurrence. The persistence of minimal residual disease (MRD) remains the primary obstacle to successful treatment outcomes. Bone marrow minimal residual disease (MRD) assessment in high-risk neuroblastoma primarily relies on the direct detection of residual tumor cells. However, the accompanying immune-microenvironmental changes remain incompletely characterized. In this study, GD2-directed immunocytochemistry, complemented by GD2-based flow cytometry, was used for the reference classification of bone marrow disease status in a cohort of 143 patients with high-risk neuroblastoma. We evaluated a panel of peripheral blood biomarkers, identifying NSE, CRP, FBG, and D-dimer as exhibiting significant differences between MRD-positive and MRD-negative groups; however, these biomarkers demonstrated limited diagnostic utility, with area under the curve (AUC) values below 0.7. Importantly, bone marrow CD14 + CD206 + M2-like monocyte-macrophages showed discriminatory ability for GD2-defined bone marrow MRD status (AUC = 0.794), with an optimal threshold of 1.71×10 4 /mL. Additionally, the proportion of CD14 + CD206 + macrophages showed a positive correlation with GD2 positivity in bone marrow samples. These findings suggest that bone marrow CD14 + CD206 + M2-like monocyte-macrophages showed potential as an auxiliary immune biomarker associated with bone marrow MRD status in high-risk NB. These findings require validation in larger, independent cohorts.