Interferon-γ (IFNγ) signaling is important for the initial response to checkpoint blockade, as highlighted by several CRISPR screens6–8 and evaluation of patients receiving CTLA-4 blockade who displayed primary or acquired resistance.9,10 These studies have found various mutations that inactivate IFNγ sensing in the tumor cells and tend to promote resistance to immunotherapy. The gene discussed is IFNG; the disease is neoplasm.