2020
CRISPR-GEMM Pooled Mutagenic Screening Identifies KMT2D as a Major Modulator of Immune Checkpoint Blockade
Wang G, Chow RD, Zhu L, Bai Z, Ye L, Zhang F, Renauer PA, Dong MB, Dai X, Zhang X, Du Y, Cheng Y, Niu L, Chu Z, Kim K, Liao C, Clark P, Errami Y, Chen S. CRISPR-GEMM Pooled Mutagenic Screening Identifies KMT2D as a Major Modulator of Immune Checkpoint Blockade. Cancer Discovery 2020, 10: 1912-1933. PMID: 32887696, PMCID: PMC7710536, DOI: 10.1158/2159-8290.cd-19-1448.Peer-Reviewed Original ResearchConceptsImmune checkpoint blockadeCheckpoint blockadeCancer typesMajority of patientsRemarkable clinical efficacyFraction of patientsMajor modulatorComplex molecular landscapeMultiple cancer typesClinical efficacyICB responseImmune infiltrationTumor immunogenicityAntigen presentationMutation burdenMouse modelPatient stratificationMutant tumorsTumor microenvironmentIssue featurePatientsTumorsMolecular landscapeBlockadeCancer
2019
In vivo CRISPR screening in CD8 T cells with AAV–Sleeping Beauty hybrid vectors identifies membrane targets for improving immunotherapy for glioblastoma
Ye L, Park JJ, Dong MB, Yang Q, Chow RD, Peng L, Du Y, Guo J, Dai X, Wang G, Errami Y, Chen S. In vivo CRISPR screening in CD8 T cells with AAV–Sleeping Beauty hybrid vectors identifies membrane targets for improving immunotherapy for glioblastoma. Nature Biotechnology 2019, 37: 1302-1313. PMID: 31548728, PMCID: PMC6834896, DOI: 10.1038/s41587-019-0246-4.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CDCD8-Positive T-LymphocytesCell Line, TumorCRISPR-Cas SystemsDependovirusFemaleGene EditingGlioblastomaHumansImmunotherapy, AdoptiveLymphocyte Activation Gene 3 ProteinMaleMembrane ProteinsMiceN-AcetylglucosaminyltransferasesNeoplasm ProteinsProtein Disulfide-IsomerasesReceptors, Cell SurfaceRNA, Guide, CRISPR-Cas SystemsTransposasesXenograft Model Antitumor AssaysConceptsRNA cassetteMembrane protein targetsPrimary murine T cellsGenetic screening systemSingle-cell sequencingScreen hitsSleeping Beauty (SB) transposonCRISPR screensMembrane proteinsCell sequencingT cellsAdeno-associated virusGenomic integrationMembrane targetsMurine T cellsProtein targetsEfficient geneHuman GBM cellsGene editingT cell receptor transgenic modelGBM cellsBeauty transposonPDIA3T cell-based immunotherapyAntigen-specific killing