Featured Publications
Immunogenetic Metabolomics Reveals Key Enzymes That Modulate CAR T-cell Metabolism and Function.
Renauer P, Park J, Bai M, Acosta A, Lee W, Lin G, Zhang Y, Dai X, Wang G, Errami Y, Wu T, Clark P, Ye L, Yang Q, Chen S. Immunogenetic Metabolomics Reveals Key Enzymes That Modulate CAR T-cell Metabolism and Function. Cancer Immunology Research 2023, 11: 1068-1084. PMID: 37253111, PMCID: PMC10527769, DOI: 10.1158/2326-6066.cir-22-0565.Peer-Reviewed Original ResearchConceptsCAR T cellsHER2-specific CAR T cellsT cellsTumor microenvironmentChimeric antigen receptor T cellsT cell-based immunotherapyAntigen receptor T cellsCD19-specific chimeric antigen receptor (CAR) T cellsCAR T-cell therapyCell-based immunotherapyReceptor T cellsT-cell therapyVivo colorectal cancer modelsColorectal cancer modelT cell functionT cell metabolismTumor infiltrationEvasion mechanismsImmunosuppressive metaboliteImmune evasionCancer modelImmunologic analysisCD19-specificUnfavorable tumor microenvironmentPDK1 deficiencyConvergent Identification and Interrogation of Tumor-Intrinsic Factors that Modulate Cancer Immunity In Vivo
Codina A, Renauer PA, Wang G, Chow RD, Park JJ, Ye H, Zhang K, Dong MB, Gassaway B, Ye L, Errami Y, Shen L, Chang A, Jain D, Herbst RS, Bosenberg M, Rinehart J, Fan R, Chen S. Convergent Identification and Interrogation of Tumor-Intrinsic Factors that Modulate Cancer Immunity In Vivo. Cell Systems 2019, 8: 136-151.e7. PMID: 30797773, PMCID: PMC6592847, DOI: 10.1016/j.cels.2019.01.004.Peer-Reviewed Original ResearchConceptsSingle-cell transcriptomic profilingExtracellular protein productionCancer cellsMutant cellsFunctional interrogationGenetic programCRISPR screensTranscriptomic profilingTumor-intrinsic mutationsTranscriptomic alterationsTumor microenvironmentProtein productionPRKAR1A lossGenetic makeupHost myeloid cellsTumor-intrinsic factorsDrastic alterationsCytometry analysisConvergent identificationMyeloid cellsCellsImmunocompetent hostsCancer immunityMutant tumorsHost
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
Multiplexed activation of endogenous genes by CRISPRa elicits potent antitumor immunity
Wang G, Chow RD, Bai Z, Zhu L, Errami Y, Dai X, Dong MB, Ye L, Zhang X, Renauer PA, Park JJ, Shen L, Ye H, Fuchs CS, Chen S. Multiplexed activation of endogenous genes by CRISPRa elicits potent antitumor immunity. Nature Immunology 2019, 20: 1494-1505. PMID: 31611701, PMCID: PMC6858551, DOI: 10.1038/s41590-019-0500-4.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigen PresentationAntigens, NeoplasmCancer VaccinesCell Line, TumorClustered Regularly Interspaced Short Palindromic RepeatsCoculture TechniquesCombined Modality TherapyDependovirusDisease Models, AnimalFemaleGene Expression Regulation, NeoplasticGenetic TherapyGenetic VectorsHEK293 CellsHumansImmunotherapyInjections, IntralesionalLymphocytes, Tumor-InfiltratingMaleMiceNeoplasmsT-Lymphocytes, CytotoxicTumor MicroenvironmentConceptsAntitumor immunityImmune responseCell-based vaccination strategiesElicits potent antitumor immunityEnhanced T cell infiltrationElicit potent immune responsesCurrent immunotherapy modalitiesStrong antitumor immunityAntitumor immune responseT cell infiltrationPotent antitumor immunityPotent immune responsesAntitumor immune signaturesMultiple cancer typesImmune signaturesImmunotherapy modalitiesTreatment modalitiesCell infiltrationVaccination strategiesTumor antigensVirus deliveryTumor microenvironmentImmunotherapyCancer typesCancer treatment