Dynamic Immune Modulation by Dendritic Cell Vaccination and IFN-α in Advanced Melanoma: Final Insights from the ABSIDE Phase II Trial

Background Advanced melanoma remains a clinical challenge despite therapeutic progress. The ABSIDE trial investigated an autologous dendritic cell vaccine (DCvax) alone or in combination with radiotherapy (RT) and/or short-course IFN-α to evaluate safety, clinical activity, and immune modulation. Methods ABSIDE is a randomized phase II trial (EudraCT 2012-001410-41). Thirty-four patients were enrolled (29 evaluable) and randomized into four arms: A (DCvax+RT), B (DCvax+IFN-α), C (DCvax+RT+IFN-α), D (DCvax alone). Peripheral blood was analyzed at baseline and during treatment by 22-plex cytokine assays, multiparametric FACS, CBC/ratios, and IFN-γ secretion assay. In situ tumor antigens expressions were assessed when tissue was available. Additionally, dendritic cell vaccine production was monitored for yield, recovery, and potency using a validated Co-Flow assay. Immunomonitoring data were analyzed at baseline and over time, and correlated with survival, disease control, and IFN-α exposure. Results Median OS varied across treatment arms (A: 5.3, B: 11.2, C: 8, D: 20.7 months). The highest immune-related disease control rate (irDCR) occurred in Arm D (57%), with positive DTH in 83% of Arm D patients and in 56% of those treated with IFN-α. Baseline profiling indicated that high CCL2, IL-4, VEGF, PMN-MDSCs, and PD-L1⁺ non-classical monocytes was associated with shorter irPFS. IFN-α pre-treatment was associated with reduced CCL2 and PD-L1⁺ non-classical monocytes. Longitudinal analysis revealed temporal trends between pre- and post-vaccination in cytokines (CXCL10, IL-2, IL-8, VEGF), blood counts (monocytes, LMR), and T-cell subsets. No significant differences emerged in the percentage of IFN-γ + specific-T cells or clinical endpoints by IFN-α status. Conclusions DC vaccination was safe and immunogenic in advanced melanoma, with the best survival and immune-related disease control observed in the DCvax-alone arm. Baseline CCL2, IL-4, VEGF, and PD-L1⁺ non-classical monocytes emerged as potential outcome biomarkers. Dynamic immune changes were induced by DCvax, but no evidence of improved clinical outcomes was observed.