Myeloid derived suppressor cells in neuroblastoma: mechanisms of immune evasion and therapeutic opportunities

Neuroblastoma is the most common extracranial pediatric solid tumor. Although the incorporation of anti-GD2 immunotherapy into standard care has improved outcomes, five-year survival for high-risk patients remains below 50%. This highlights that, while immunotherapy holds promise in this pediatric cancer, neuroblastoma has developed multiple immunosuppressive mechanisms that limit anti-tumor immune responses. Among these, myeloid cells, including tumor associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs) play a central role in promoting tumor progression and suppressing immune activity. MDSCs, which are primarily classified into monocytic (M-MDSC) and granulocytic (PMN-MDSC) subsets, are markedly increased in both murine neuroblastoma models and human patients, where they promote immunosuppression and impair T cell and NK cell functions. This review summarizes the myeloid landscape in neuroblastoma, covering the origin and development of MDSCs, the phenotypic and functional diversity of MDSC subsets, the mechanisms driving MDSC recruitment and immunosuppressive activity, and emerging therapeutic strategies to enhance immunotherapy efficacy, including approaches to target MDSCs and modulate ferroptosis to reprogram their function.