Association of SCART1+ T cells with neutrophils and cytokine-mediated induction of immunosuppressive neutrophils in neuroblastoma

Neuroblastoma (NB) is a pediatric solid tumor with poor outcomes in high-risk cases, largely driven by the tumor microenvironment (TME). Tumor-associated neutrophils (TANs) exert potent regulatory effects within the TME, but the mechanisms orchestrating their activation and functional polarization in NB remain elusive. Here, utilizing proteomic and single-cell transcriptomic analyses, we identify a distinct tumor-enriched SCART1+ T cell subset within the NB TME. This population prominently secretes IL-17 A, GM-CSF, IL-22, and TNF-α. Moreover, the abundance of SCART1+ T cells correlates positively with TAN infiltration. Further functional assays reveal that IL-17 A and GM-CSF promote neutrophil migration, while GM-CSF and TNF-α induce neutrophil activation and immunosuppression. Collectively, our data demonstrate that the specific cytokines are capable of driving the recruitment and immunosuppressive polarization of neutrophils in NB TME. These findings suggest SCART1+ T cells as potential architects of neutrophil suppressive polarization via a cytokine-mediated network, representing a promising target for immunotherapy.