Systematic Immunotherapy Target Discovery Using Genome-Scale In Vivo CRISPR Screens in CD8 T Cells
Dong MB, Wang G, Chow RD, Ye L, Zhu L, Dai X, Park JJ, Kim HR, Errami Y, Guzman CD, Zhou X, Chen KY, Renauer PA, Du Y, Shen J, Lam SZ, Zhou JJ, Lannin DR, Herbst RS, Chen S. Systematic Immunotherapy Target Discovery Using Genome-Scale In Vivo CRISPR Screens in CD8 T Cells. Cell 2019, 178: 1189-1204.e23. PMID: 31442407, PMCID: PMC6719679, DOI: 10.1016/j.cell.2019.07.044.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBreast NeoplasmsCD8-Positive T-LymphocytesCell Line, TumorClustered Regularly Interspaced Short Palindromic RepeatsCytokinesFemaleHumansImmunologic MemoryImmunotherapyMaleMiceMice, KnockoutNF-kappa BProgrammed Cell Death 1 ReceptorRNA HelicasesRNA, Guide, CRISPR-Cas SystemsTranscriptomeConceptsCRISPR screensTarget discoveryGenome-scale CRISPR screensCD8 TRNA helicase DHX37Vivo CRISPR screensGenetic screenGenome scaleTranscriptomic profilingBiochemical interrogationAntigen-specific CD8 TAnti-tumor immune responseFunctional regulatorTriple-negative breast cancerDHX37Essential roleTim-3PD-1Cytokine productionTumor infiltrationImmunotherapy targetImmunotherapy settingsRegulatorBreast cancerT cellsPrecise spatio-temporal interruption of regulatory T cell-mediated CD8+ T cell suppression leads to tumor immunity
Zhou X, Zhao S, He Y, Geng S, Shi Y, Wang B. Precise spatio-temporal interruption of regulatory T cell-mediated CD8+ T cell suppression leads to tumor immunity. Cancer Research 2019, 79: canres.1250.2018. PMID: 30254146, DOI: 10.1158/0008-5472.can-18-1250.Peer-Reviewed Original ResearchConceptsTumor-draining lymph nodesRegulatory T cellsT cellsStrong tumor-suppressive effectSphingosine-1-phosphate receptor 1Low systemic side effectsT cell activityT cell suppressionSignificant tumor reductionSystemic side effectsAntitumor immune activationTumor-suppressive effectsDraining lymphMinimal blockadeTreg ablationTreg inhibitionLymph nodesTumor immunityTumor inoculationClinical evidenceImmune activationImmune suppressionTumor reductionCD8Cell suppression