Interferon-α2b(University Hospital Tuebingen)

While recent advances in immuno-oncology have revolutionized cancer therapy, only a subset patients benefit from these treatments and achieve durable clinical responses. Biomarker-guided identification of patients likely to respond to immunotherapy could enable more effective management of various malignancies. To explore this, we took advantage of a Phase I trial evaluating the efficacy of antigen-engineered dendritic cell (DC) vaccine, administered either as monotherapy or in combination with high-dose interferon-α2b, in promoting anti-tumor immunity in melanoma patients. Liquid biopsies, including serum and peripheral blood mononuclear cells, and tumor biopsies were previously analyzed for predictive markers using Luminex, NanoString gene expression profiling and flow cytometry. Here, in vitro stimulation assays were conducted to assess arginase-1 production by circulating myeloid subsets. Of 73 serum analytes, serum arginase-1 (sArg1) most effectively distinguished melanoma patients with measurable disease from healthy donors. Elevated sArg1 levels in patients with active disease correlated with favorable responses to the vaccine and were associated with longer overall and progression-free survival. Integrated phenotypic, functional and metabolic analyses identified circulating CD14^-CD11c⁺ DC3 as the likely source of sArg1. These findings support the hypothesis that sArg1 may serve as a biomarker for responsiveness to cancer vaccine immunotherapy and reflect systemic myeloid cell fitness associated with enhanced anti-tumor immunity. Given the stability and accessibility of serum compared to cells or tissues, this assay could offer a method for assessing patient status, potentially improving stratification and clinical decision-making.