2022
A genome-scale gain-of-function CRISPR screen in CD8 T cells identifies proline metabolism as a means to enhance CAR-T therapy
Ye L, Park JJ, Peng L, Yang Q, Chow RD, Dong MB, Lam SZ, Guo J, Tang E, Zhang Y, Wang G, Dai X, Du Y, Kim HR, Cao H, Errami Y, Clark P, Bersenev A, Montgomery RR, Chen S. A genome-scale gain-of-function CRISPR screen in CD8 T cells identifies proline metabolism as a means to enhance CAR-T therapy. Cell Metabolism 2022, 34: 595-614.e14. PMID: 35276062, PMCID: PMC8986623, DOI: 10.1016/j.cmet.2022.02.009.Peer-Reviewed Original ResearchConceptsCAR T cellsT cell-based immunotherapyRight molecular targetCell-based immunotherapyCAR-T therapyChimeric antigen receptorMultiple cancer modelsCAR-T efficacyFunction CRISPR screensCD8 TPrimary CD8Immune functionImmunological diseasesImmune boosterCancer modelAntigen receptorDistinct gene expressionMolecular targetsCRISPR activation screensMetabolic programsImmunological analysisTherapyCancerEfficacyActivation screens
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
2018
Sno-derived RNAs are prevalent molecular markers of cancer immunity
Chow RD, Chen S. Sno-derived RNAs are prevalent molecular markers of cancer immunity. Oncogene 2018, 37: 6442-6462. PMID: 30072739, PMCID: PMC6294694, DOI: 10.1038/s41388-018-0420-z.Peer-Reviewed Original ResearchConceptsCancer immunityCytolytic T cell activityCancer typesHuman cancer immunityTumor immune signatureT cell infiltrationT cell activityTumor immune microenvironmentHuman cancersClinical outcomesImmunosuppressive markersPatient survivalCell infiltrationDistinct cancer typesTumor vasculatureCell activityPatient samplesExpression signaturesImmunityCancerMarkersMolecular markersLike propertiesSdRNAsLarge panel