Extended Data Fig. 5: MHC-I is a potential immune inhibitory ligand downstream of IFN.

a, Scatter plot of IFNγ-induced gene expression change (x-axis) by enrichment or depletion in WT vs NSG comparison across in vivo screens (y-axis) for all genes included in the genome-scale screening library. Dot size indicates aggregate screen score. b, Gene expression fold change of NK ligands, IFN signaling pathway, antigen processing and presentation machinery, classical and non-classical class I MHC, and immune inhibitory receptor genes in IFNγ or IFNβ stimulation compared to baseline expression. c, Histograms showing cell surface expression of H2-K, H-2D, Qa-1^b or PD-L1 measured by flow cytometry on CT26 and KPC cells with (red) and without (grey) IFNβ stimulation. d, Histograms showing cell surface expression of H2-D^b and H2-K^b on KPC Cas9 cells transduced with control, Tap1, or Jak1 sgRNA and cultured with or without IFNγ in vitro. e, Log fold change in the ratio of tumor cells with sgRNAs targeting Ifngr1 or Jak1 vs control sgRNA within CT26 tumors in a control (grey) or Tap1-null (purple) genetic background, normalized to the ratio for tumors implanted in NSG mice (Ifngr1 No Tx: p = 0.0014; Jak1 No Tx: p < 0.0001; anti-PD-1: p = 0.003). Experiments were conducted using n ≥ 5 mice/group from at least two independent experiments. Data in bar plots are presented as mean ± SEM. **p < 0.01, ****p < 0.0001 [unpaired, two-sided Student’s t-test].