2024
Deleting the mitochondrial respiration negative regulator MCJ enhances the efficacy of CD8+ T cell adoptive therapies in pre-clinical studies
Wu M, Valenca-Pereira F, Cendali F, Giddings E, Pham-Danis C, Yarnell M, Novak A, Brunetti T, Thompson S, Henao-Mejia J, Flavell R, D’Alessandro A, Kohler M, Rincon M. Deleting the mitochondrial respiration negative regulator MCJ enhances the efficacy of CD8+ T cell adoptive therapies in pre-clinical studies. Nature Communications 2024, 15: 4444. PMID: 38789421, PMCID: PMC11126743, DOI: 10.1038/s41467-024-48653-y.Peer-Reviewed Original ResearchConceptsMethylation-controlled J proteinCAR-T cellsEfficacy of adoptive T cell therapyCD8+ CAR T cellsAdoptive T cell therapyT-cell therapyCD8 cellsT cellsOvalbumin (OVA)-specific CD8T cell adoptive therapyCD8+ T cellsMelanoma tumors in vivoFunction of T cellsAdoptive cellular therapyMurine B-cell leukemiaPromote T cell functionB-cell leukemiaT cell functionTumors in vivoPre-clinical studiesAnti-tumor activityIn vivo efficacyAdoptive therapyPotential therapeutic strategyEndogenous negative regulator
2023
IL-7R licenses a population of epigenetically poised memory CD8+ T cells with superior antitumor efficacy that are critical for melanoma memory
Micevic G, Daniels A, Flem-Karlsen K, Park K, Talty R, McGeary M, Mirza H, Blackburn H, Sefik E, Cheung J, Hornick N, Aizenbud L, Joshi N, Kluger H, Iwasaki A, Bosenberg M, Flavell R. IL-7R licenses a population of epigenetically poised memory CD8+ T cells with superior antitumor efficacy that are critical for melanoma memory. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2304319120. PMID: 37459511, PMCID: PMC10372654, DOI: 10.1073/pnas.2304319120.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigensCD8-Positive T-LymphocytesHumansImmunologic MemoryLicensureMelanomaMemory T CellsMiceSignal TransductionConceptsIL-7R expressionT cellsIL-7RAntitumor memorySuperior antitumor efficacyCell-based therapiesTumor-specific T cellsAntigen-specific T cellsAntitumor efficacyPowerful antitumor immune responseMarkers of exhaustionTumor-specific CD8Antitumor immune responseIndependent prognostic factorAntitumor immune memoryMemory T cellsMajor risk factorSuperior antitumor activityFunctional CD8Memory CD8Prognostic factorsSurgical resectionAdvanced melanomaLymph nodesNaive mice
2022
Platelet-derived TLT-1 promotes tumor progression by suppressing CD8+ T cells
Tyagi T, Jain K, Yarovinsky TO, Chiorazzi M, Du J, Castro C, Griffin J, Korde A, Martin KA, Takyar SS, Flavell RA, Patel AA, Hwa J. Platelet-derived TLT-1 promotes tumor progression by suppressing CD8+ T cells. Journal Of Experimental Medicine 2022, 220: e20212218. PMID: 36305874, PMCID: PMC9814191, DOI: 10.1084/jem.20212218.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlood PlateletsCarcinoma, Non-Small-Cell LungCD8-Positive T-LymphocytesLung NeoplasmsMiceReceptors, ImmunologicConceptsCD8 T cellsT cellsTLT-1Non-small cell lung cancer patientsCell lung cancer patientsTREM-like transcript-1Tumor immunosuppressive mechanismsT cell suppressionLung cancer patientsPatient T cellsNF-κB pathwayPatient-derived tumorsDistinct activation phenotypesNSCLC patientsImmunosuppressive mechanismsSyngeneic tumorsHumanized miceImmunoregulatory rolePrognostic significanceImmunocompetent miceCancer patientsCell suppressionActivation phenotypeReduced tumorTumor growth
1994
Thymic development in human CD4 transgenic mice. Positive selection occurs after commitment to the CD8 lineage.
Paterson RK, Burkly LC, Kurahara DK, Dunlap A, Flavell RA, Finkel TH. Thymic development in human CD4 transgenic mice. Positive selection occurs after commitment to the CD8 lineage. The Journal Of Immunology 1994, 153: 3491-503. PMID: 7930572, DOI: 10.4049/jimmunol.153.8.3491.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCD4 AntigensCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesFemaleHistocompatibility Antigens Class IHistocompatibility Antigens Class IIHumansMaleMiceMice, Inbred C57BLMice, TransgenicReceptors, Antigen, T-CellSelection, GeneticStochastic ProcessesT-Lymphocyte SubsetsThymus Gland