Using in vivo mouse models, Benci et al. showed that prolonged IFNγ signaling in tumor cells can augment the expression of IFN-stimulated genes and ligands for multiple T-cell inhibitory receptors on tumor cells, which increases PD-L1-dependent and PD-L1-independent resistance to immune checkpoint blockage through multiple inhibitory pathways. This evidence concerns the gene IFNA1 and neoplasm.