Generation of murine tumor models refractory to immune checkpoint inhibitors using CRISPR/Cas9

We demonstrate a CRISPR/Cas9 approach for the generation of murine solid tumor models refractory to ICB due to APM/IFN signaling defects. Guide RNAs were employed to delete B2m, Jak1, or Psmb9 genes in EMT6 breast tumor cells. This pipeline enables the generation of unique solid tumor models to fast track the discovery of alternative therapies for patients harboring innate or acquired resistance to ICB.