Biochimica et Biophysica Acta Reviews on Cancer · Nov 4, 2026

Cellular senescence remodels the neuro-immune-tumour niche in neuroblastoma through SASP and core signalling pathways

By Zhang Z, Zhang X

Neuroblastoma (NB), the most common extracranial solid tumour in children, presents a stark clinical dichotomy: stage 4S disease may spontaneously regress, whereas high-risk patients face persistently high relapse and mortality rates despite intensive therapy. This suggests that the tumour microenvironment (TME) critically governs disease trajectory. Cellular senescence, a stress-responsive cell fate, has been increasingly implicated in NB, yet its dual pro- and anti-tumourigenic roles remain unclear. Senescence is not uniform; rather, distinct induction conditions generate divergent senescence-associated secretory phenotypes (SASPs), which exert context-dependent paracrine effects on neural, immune, and tumour cells within the TME. This review examines how senescence-driven SASP may remodel the neuro-immune-tumour microenvironment. We outline the triggers and cellular origins of senescence, characterize SASP composition and transcriptional control, and describe its potential multifaceted effects on immune reprogramming, neuroinflammation, and tumour progression. Integrating PI3K/Akt/mTOR and autophagy-apoptosis signalling, along with adjacent neurogenic signals such as SP/NK-1R, we hypothesize that the contrasting outcomes of 4S versus high-risk disease reflect alternative fate switches among senescence, autophagy, and apoptosis. We also summarize emerging senolytic, senomorphic, and neuroimmune-targeted strategies, along with their clinical prospects. A deeper understanding of senescence heterogeneity in neuroblastoma may offer both biological insights and new therapeutic avenues.

doi.org/10.1016/j.bbcan.2026.189750 Open access PubMed 42982106 Mechanisms