Low regulatory T-cells are associated with improved survival of neuroblastoma patients treated with anti-GD2 antibodies

Immunotherapies with anti-GD2 antibodies (Abs) have improved survival of high-risk neuroblastoma (NB) patients (pts). In a closed single-center program, 53 pts received 5 cycles of 6 × 106 IU/m2 subcutaneous IL-2 (d1 – 5; 8 – 12) combined with long-term infusion (LTI) of 100 mg/m2 of the anti-GD2 Ab ch14.18/CHO (d8 – 18). Cytotoxic NK-, regulatory T cells (Tregs) and neutrophils were analyzed by flow cytometry. IFN-γ, IL-6, IL-10, IL-18 and CCL2 serum concentrations were measured using bead-based immunoassays. All data were correlated with PFS. IL-2 administration increased cytotoxic NK- and Treg cell counts in cycle 1 followed by further increase in subsequent cycles, whereas neutrophil levels were elevated only after the Ab infusion. Levels of IFN-γ, IL-6, IL-10, IL-18 and CCL2 were increased after the combined therapy. Importantly, pts with low Treg levels had significantly improved PFS compared to pts with high levels. Notably, Treg counts negatively correlated with INF-γ concentrations. In conclusion, LTI of ch14.18/CHO in combination with IL-2 resulted in Treg induction that negatively correlated with IFN-γ release and PFS.