Our study shows that re-education of tumor-associated macrophages by tumoral IFNβ translates into improved clinical outcome in patients with melanoma brain metastases, providing pathomechanistic insights into synergistic type I interferon–inducing therapies with immunotherapies and warranting investigation of IFNβ as a predictive biomarker for combined radioimmunotherapy. This evidence concerns the gene IFNB1 and neoplasm.