To address these issues, we generated a melanoma model with knockout of the IFN-γ signaling by deleting IFNγR1 from B16-BL6 cells using the CRISPR-Cas9 technology (IFNγR1KO).12 We first confirmed that IFNγR1KO cells were defective of IFN-γ signaling, reflected by their lack of IFN-γ-induced upregulation of IRF-1 (a direct transcriptional target of IFN-γ), PD-L1 expression, and cell killing. Here, IFNG is linked to melanoma.