biostudies-literatureUnknown29(6)Li MFoundation for Innovative Research Groups of the National Natural Science Foundation of ChinaGenome-wide clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated 9 (Cas9)-mediated loss-of-function screens are powerful tools for identifying genes responsible for diverse phenotypes. Here, we perturbed genes in melanoma cells to screen for genes involved in tumor escape from T cell-mediated killing. Multiple interferon gamma (IFNγ) signaling-related genes were enriched in melanoma cells resistant to T cell killing. In addition, deletion of the deubiquitinating protease ubiquitin specific peptidase 22 (USP22) in mouse melanoma (B16-OVA) cells decreased the efficacy of T cell-mediated killing, both in vitro and in vivo, while overexpression enhanced tumor-cell sensitivity to T (OT-I) cell-mediated killing. USP22 deficiency in both mouse and human melanoma ceMolecular therapy : the journal of the American Society of Gene Therapy2108-2120https://www.ebi.ac.uk/biostudies/studies/S-EPMC8178440biostudies-literatureUSP22 deficiency in melanoma mediates resistance to T cells through IFNγ-JAK1-STAT1 signal axis.PMC8178440Yang XHan PQi XLiang JLi FGao YLin HLi MXu YfalseUSP22 deficiency in melanoma mediates resistance to T cells through IFNγ-JAK1-STAT1 signal axis.Genome-wide clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated 9 (Cas9)-mediated loss-of-function screens are powerful tools for identifying genes responsible for diverse phenotypes. Here, we perturbed genes in melanoma cells to screen for genes involved in tumor escape from T cell-mediated killing. Multiple interferon gamma (IFNγ) signaling-related genes were enriched in melanoma cells resistant to T cell killing. In addition, deletion of the deubiquitinating protease ubiquitin specific peptidase 22 (USP22) in mouse melanoma (B16-OVA) cells decreased the efficacy of T cell-mediated killing, both in vitro and in vivo, while overexpression enhanced tumor-cell sensitivity to T (OT-I) cell-mediated killing. USP22 deficiency in both mouse and human melanoma ce2021-01-01T00:00:00Z2021 Jun2025-04-19T18:17:56.148Z2025-04-19T18:17:56.148ZS-EPMC81784403360105310.1016/j.ymthe.2021.02.018