2024
The type 2 cytokine Fc–IL-4 revitalizes exhausted CD8+ T cells against cancer
Feng B, Bai Z, Zhou X, Zhao Y, Xie Y, Huang X, Liu Y, Enbar T, Li R, Wang Y, Gao M, Bonati L, Peng M, Li W, Tao B, Charmoy M, Held W, Melenhorst J, Fan R, Guo Y, Tang L. The type 2 cytokine Fc–IL-4 revitalizes exhausted CD8+ T cells against cancer. Nature 2024, 634: 712-720. PMID: 39322665, PMCID: PMC11485240, DOI: 10.1038/s41586-024-07962-4.Peer-Reviewed Original ResearchCD8+ T cellsMammalian target of rapamycinCancer immunotherapyT cellsNext-generation cancer immunotherapyAdoptive T-cell transferImmune checkpoint blockade therapyLong-term complete remissionCurrent cancer immunotherapiesCheckpoint blockade therapyInduce durable remissionsT-cell transferCD8+ TCytokine-based immunotherapyType 2 cytokinesXenograft tumor modelBlockade therapyDurable remissionsComplete remissionAntitumour efficacyTumor modelTarget of rapamycinInterleukin-4Immune responseCD8Single-cell CAR T atlas reveals type 2 function in 8-year leukaemia remission
Bai Z, Feng B, McClory S, de Oliveira B, Diorio C, Gregoire C, Tao B, Yang L, Zhao Z, Peng L, Sferruzza G, Zhou L, Zhou X, Kerr J, Baysoy A, Su G, Yang M, Camara P, Chen S, Tang L, June C, Melenhorst J, Grupp S, Fan R. Single-cell CAR T atlas reveals type 2 function in 8-year leukaemia remission. Nature 2024, 634: 702-711. PMID: 39322664, PMCID: PMC11485231, DOI: 10.1038/s41586-024-07762-w.Peer-Reviewed Original ResearchChimeric antigen receptorChimeric antigen receptor T cellsT cellsIL-4CAR T-cell dysfunctionChimeric antigen receptor T-cell productsCAR-T cell persistenceProteomic profiling of seraCAR-T cellsT cell persistenceT-cell therapyLong-term remissionT cell dysfunctionCAR-T productsType 2 cytokinesAntigen-specific activationT cell productionAssociated with patientsType 2 cellsDysfunctional subsetPotential therapeutic strategyCellular immunotherapyLeukemia remissionPatients relapseType 2 functions
2023
Single-Cell Multi-Omics Reveals Type-2 Functionality in Maintaining CAR T Cell Longevity Associated with 8-Year Leukemia Remission
Bai Z, Feng B, Mcclory S, Diorio C, Zhao Z, Tang L, Melenhorst J, June C, Grupp S, Fan R. Single-Cell Multi-Omics Reveals Type-2 Functionality in Maintaining CAR T Cell Longevity Associated with 8-Year Leukemia Remission. Blood 2023, 142: 352. DOI: 10.1182/blood-2023-179480.Peer-Reviewed Original ResearchChimeric antigen receptor T cellsCAR-T cellsChimeric antigen receptorType 2 cytokinesB-cell aplasiaT cellsAcute lymphocytic leukemiaCAR-T persistenceIL-4CAR-TType 1Validation cohortCAR T infusionSurvival of tumor-bearing miceDiscovery cohortPersistent CAR T cellsDose of tumor cellsLevels of type 2 cytokinesType 2 cytokine levelsNSG mouse modelPediatric ALL patientsLong-term remissionReduced tumor burdenT cell longevityType 1 cytokinesPrior cycles of anti-CD20 antibodies affect antibody responses after repeated SARS-CoV-2 mRNA vaccination
Asashima H, Kim D, Wang K, Lele N, Buitrago-Pocasangre N, Lutz R, Cruz I, Raddassi K, Ruff W, Racke M, Wilson J, Givens T, Grifoni A, Weiskopf D, Sette A, Kleinstein S, Montgomery R, Shaw A, Li F, Fan R, Hafler D, Tomayko M, Longbrake E. Prior cycles of anti-CD20 antibodies affect antibody responses after repeated SARS-CoV-2 mRNA vaccination. JCI Insight 2023, 8: e168102. PMID: 37606046, PMCID: PMC10543713, DOI: 10.1172/jci.insight.168102.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 mRNA vaccinationB-cell-depleted patientsB-cell depletionAntibody responseMRNA vaccinationThird doseCell depletionT cellsClaude D. Pepper Older Americans Independence CenterB cellsNational Multiple Sclerosis SocietyAnti-CD20 antibodySpike-specific antibodiesMultiple Sclerosis SocietyLow cumulative exposureLogistic regression modelsImportant clinical needCD20 therapyCD20 treatmentMost patientsThird vaccineSerologic responseVaccine dosesMRNA vaccinesVaccination strategies
2017
Single-cell cytokine profiling of tumor-infiltrating T cells to measure patient responses to anti-PD-1 therapy.
Mackay S, Flynn B, Morse K, Paczkowski P, Bacchiocchi A, Fan R, Halaban R, Zhou J. Single-cell cytokine profiling of tumor-infiltrating T cells to measure patient responses to anti-PD-1 therapy. Journal Of Clinical Oncology 2017, 35: 49-49. DOI: 10.1200/jco.2017.35.7_suppl.49.Peer-Reviewed Original ResearchTumor-infiltrating T lymphocytesAnti-PD-1 therapyClinical outcomesCytokine profilingAnti-tumor T cell functionAnti-tumor T cell immunityTumor-infiltrating T cellsMIP-1 αAnti-tumor immunityT cell immunityResponse of patientsT cell functionCell immunityCheckpoint immunotherapyMelanoma patientsIL-8Metastatic melanomaCancer patientsTIL functionTIL analysisPatient responseT cellsT lymphocytesGranzyme BImmune function
2016
AI-22 Single cell protein and transcriptional profiling of CD4+ follicular B helper T (TFH) and central memory (TCM) cells in SLE: physiological and pathological phenotypes
Kwak M, Choi J, Kim S, Chen Z, Lee G, Craft J, Fan R. AI-22 Single cell protein and transcriptional profiling of CD4+ follicular B helper T (TFH) and central memory (TCM) cells in SLE: physiological and pathological phenotypes. Lupus Science & Medicine 2016, 3: a11. DOI: 10.1136/lupus-2016-000179.22.Peer-Reviewed Original ResearchCentral memory cellsTCM cellsTfh cellsSLE patientsHealthy donorsT cellsFollicular B helper T cellsSystemic lupus erythematosusCirculation of patientsHelper T cellsSLE T cellsLupus kidneysHumoral autoimmunityTranscriptional profilingIL-21Lupus erythematosusCytokine producersHelper TMurine lupusHumoral immunityLymphoid organsEnd organsLupus researchPathological outcomesTherapeutic target