Neuroblastoma (NB)

which is the most common pediatric extracranial solid tumor

varies widely in its clinical presentation and outcome. NB has a unique ability to spontaneously differentiate and regress

suggesting a potential direction for therapeutic intervention. However

the underlying mechanisms of regression remain largely unknown

and more reliable prognostic biomarkers are needed for predicting trajectories for NB. We performed scRNA-seq analysis on 17 NB clinical samples and three peritumoral adrenal tissues. Primary NB displayed varied cell constitution

even among tumors of the same pathological subtype. Copy number variation patterns suggested that neuroendocrine cells represent the malignant cell type. Based on the differential expression of sets of related marker genes

a subgroup of neuroendocrine cells was identified and projected to differentiate into a subcluster of benign fibroblasts with highly expressed

CCL2

and

ZFP36

supporting a progressive pathway of spontaneous NB regression. We also identified prognostic markers (

STMN2

TUBA1A

PAGE5

and

ETV1

) by evaluating intra-tumoral heterogeneity. Lastly

we determined that

ITGB1

in M2-like macrophages was associated with favorable prognosis and may serve as a potential diagnostic marker and therapeutic target. In conclusion

our findings reveal novel mechanisms underlying regression and potential prognostic markers and therapeutic targets of NB.