Irinotecan Modulates Immune Checkpoints in Neuroblastoma

Neuroblastoma (NBL) is the most common extracranial solid tumor in children, with a 50% survival rate in high-risk cases. Chemotherapy combination with immunotherapy is central to HR-NBL treatment.

This study aimed to explore how Irinotecan influences the immune landscape of NBL cells, particularly focusing on the modulation of immune checkpoints relevant to future chemo-immunotherapy strategies.

Two neuroblastoma cell lines, SK-N-BE(2) and SH-SY5Y, were exposed to sub-lethal doses of Irinotecan and IFN-γ. Flow cytometry assessed the expression of immune markers, including GD2, CD47, MHC I, and PD-L1. We also examined phagocytosis by macrophages and T-cell-mediated killing. In vivo studies using a neuroblastoma mouse model assessed the effects of Irinotecan and PBMC injections. Soluble CD47 was also measured in cell culture supernatants and exploratory patient plasma samples.

Treatment exposure was associated with modulation of several immune-related markers, including GD2, CD47, PD-L1, and MHC class I. While Irinotecan reduced macrophage-mediated phagocytosis, this effect was reversed by the addition of anti-CD47 antibodies. T-cell-mediated killing was enhanced when NBL cells were pre-treated with Irinotecan. In vivo studies showed that the combination of PBMCs and Irinotecan resulted in reduced tumor burden compared to either treatment alone. Furthermore, CD47 expression was detectable in-patient plasma, suggesting that soluble CD47 may warrant exploration in larger future cohorts.

This pilot study suggests that irinotecan may modulate key immune checkpoints in neuroblastoma. These results supports further investigation of rational chemo-immunotherapy combinations, including GD2 and CD47-targeted combination strategies.