Autoantibodies associate with clinical outcome in patients with melanoma treated with a dendritic cell-based vaccine

Increased B cell receptor signaling pathways in patients with melanoma correlates with a favorable clinical response to a cancer vaccine expressing multiple tumor-associated antigens. Here, we utilize phage immunoprecipitation sequencing (PhIP-seq) and Rapid Extracellular Antigen Profiling (REAP) assays to analyze the autoantibody profiles of patients with melanoma from a dendritic cell vaccine trial (NCT01622933), before and after vaccination. Patients have significantly elevated breadth and titer of autoantibodies compared to healthy donors. Vaccination results in the induction of de novo autoantibodies, particularly those with a favorable clinical outcome. Reduced serum SDF1-alpha, MIP-1ß, MCP1 and increased circulating monocytes are associated with development of autoantibodies. We identify plasma autoantibody signatures separating melanoma from healthy subjects as well as clinical responders vs non-responders to vaccination treatment. These findings demonstrate the potential for autoantibodies as diagnostic and prognostic biomarkers that predict clinical outcomes in cancer. NCT01622933 was a clinical trial of an autologous dendritic cell-based vaccine in patients with melanoma. Here the authors show that the vaccine results in the induction of de novo autoantibodies associated with a favourable clinical outcome.