2023
CTLA-4 tail fusion enhances CAR-T antitumor immunity
Zhou X, Cao H, Fang S, Chow R, Tang K, Majety M, Bai M, Dong M, Renauer P, Shang X, Suzuki K, Levchenko A, Chen S. CTLA-4 tail fusion enhances CAR-T antitumor immunity. Nature Immunology 2023, 24: 1499-1510. PMID: 37500885, PMCID: PMC11344484, DOI: 10.1038/s41590-023-01571-5.Peer-Reviewed Original ResearchConceptsCytoplasmic tailSingle-cell RNA sequencingRNA sequencingC-terminusTail fusionCell engineering techniquesAntigen receptorFurther characterizationCytometry analysisSurface expressionCAR functionLow surface expressionCellsUnique strategyT cellsPowerful therapeuticsFusionEndocytosisLeukemia modelTerminusTailSequencingPhenotypeReduced activationEngineering techniques
2019
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
2017
Analysis of immunological mechanisms exerted by HBsAg-HBIG therapeutic vaccine combined with Adefovir in chronic hepatitis B patients
Zhou C, Li C, Gong G, Wang S, Zhang J, Xu D, Guo L, Ren H, Xu M, Xie Q, Pan C, Xu J, Hu Z, Geng S, Zhou X, Wang X, Zhou X, Mi H, Zhao G, Yu W, Wen Y, Huang L, Wang X, Wang B. Analysis of immunological mechanisms exerted by HBsAg-HBIG therapeutic vaccine combined with Adefovir in chronic hepatitis B patients. Human Vaccines & Immunotherapeutics 2017, 13: 1989-1996. PMID: 28665747, PMCID: PMC5612521, DOI: 10.1080/21645515.2017.1335840.Peer-Reviewed Original ResearchMeSH KeywordsAdenineAdjuvants, ImmunologicAdultAntigen-Antibody ComplexCombined Modality TherapyFemaleHepatitis B Surface AntigensHepatitis B VaccinesHepatitis B, ChronicHumansInterleukin-10Interleukin-17Interleukin-2MaleOrganophosphonatesTh1 CellsTh2 CellsTransforming Growth Factor betaTumor Necrosis Factor-alphaYoung AdultConceptsChronic hepatitis B patientsHepatitis B patientsT cellsImmunized groupsB patientsImmunological mechanismsTherapeutic vaccinesHost-specific immune responseIL-2 levelsSero-conversion rateSpecific immune responseEarly inflammatory responseCHB patientsTc17 cellsTreg cellsCytokine profileIL-17AIL-10Saline groupCell CD4More injectionsAdjuvant controlsClinical trialsInflammatory responseNormal salineInduced Regulatory T Cells Superimpose Their Suppressive Capacity with Effector T Cells in Lymph Nodes via Antigen-Specific S1p1-Dependent Egress Blockage
Geng S, Zhong Y, Zhou X, Zhao G, Xie X, Pei Y, Liu H, Zhang H, Shi Y, Wang B. Induced Regulatory T Cells Superimpose Their Suppressive Capacity with Effector T Cells in Lymph Nodes via Antigen-Specific S1p1-Dependent Egress Blockage. Frontiers In Immunology 2017, 8: 663. PMID: 28638384, PMCID: PMC5461288, DOI: 10.3389/fimmu.2017.00663.Peer-Reviewed Original ResearchEffector T cellsLymph nodesT cellsInduced Regulatory T CellsAntigen-specific mechanismsAntigen-specific TregsHilar lymph nodesRegulatory T cellsAirway inflammationSuppression targetsSuppressive capacityAntigen stimulationReceptor expressionPeripheral generationTherapeutic programSame receptorTregsOptimal inhibitionInflammationCellsAsthmaS1P1AllergensReceptors