Inhibition of CDK1 Promotes Immunogenic Cell Death in Neuroblastoma.

BACKGROUND: Neuroblastoma is characterized by multiple immune evasion strategies, making it critical to explore the use of immunotherapy. CDK1 is known for its role in regulating cell cycle progression and is aberrantly expressed in various tumors, yet its role in NB and immunogenic cell death remains unclear. METHODS: We investigated the association between the expression of CDK1 and the outcome of neuroblastoma according to the TCGA database and confirmed the results by tissue arrays. Furthermore, we evaluated the correlation between CDK1 expression and immune cell infiltration as well as cytokine effectiveness. Finally, in vitro and in vivo experiments were used to confirm the effects of a CDK1 inhibitor. RESULTS: CDK1 was overexpressed in advanced neuroblastoma and was associated with poor prognosis. High CDK1 expression correlated with reduced immune cell infiltration and decreased levels of effector cytokines including IL-12, IFN-γ, and IRF1. Furthermore, the inhibition of CDK1 slowed the growth of neuroblastoma cells and promoted immunogenic cell death in neuroblastoma. CDK1 inhibition via RO-3306 suppressed tumor growth and induced hallmark features of ICD, including CRT exposure, HSP70 expression, and HMGB1 release. CONCLUSION: CDK1 inhibition not only slows neuroblastoma progression but also triggers DAMP release consistent with ICD and immune activation. CDK1 may be a potential prognostic marker and effective treatment target for improving immunotherapy efficacy in neuroblastoma patients.