2018
Tumor-specific MHC-II expression drives a unique pattern of resistance to immunotherapy via LAG-3/FCRL6 engagement
Johnson DB, Nixon MJ, Wang Y, Wang DY, Castellanos E, Estrada MV, Ericsson-Gonzalez PI, Cote CH, Salgado R, Sanchez V, Dean PT, Opalenik SR, Schreeder DM, Rimm DL, Kim JY, Bordeaux J, Loi S, Horn L, Sanders ME, Ferrell PB, Xu Y, Sosman JA, Davis RS, Balko JM. Tumor-specific MHC-II expression drives a unique pattern of resistance to immunotherapy via LAG-3/FCRL6 engagement. JCI Insight 2018, 3: e120360. PMID: 30568030, PMCID: PMC6338319, DOI: 10.1172/jci.insight.120360.Peer-Reviewed Original ResearchMeSH KeywordsAdaptive ImmunityAnimalsAntibodies, NeutralizingAntigens, CDBreast NeoplasmsCD4-Positive T-LymphocytesCell Line, TumorHistocompatibility Antigens Class IIHLA-DR AntigensHumansImmunotherapyKiller Cells, NaturalLigandsLymphocyte Activation Gene 3 ProteinMiceProgrammed Cell Death 1 ReceptorReceptors, Antigen, T-CellReceptors, Cell SurfaceT-LymphocytesTumor MicroenvironmentConceptsMHC-II expressionT cellsAnti-PD-1 therapyTumor cellsPD-1 pathwayTumor-intrinsic factorsPD-1-targeted immunotherapiesMHC-II receptorsDurable responsesPD-1Immune activationImmunotherapy targetPreclinical modelsLAG-3TumorsUnique patternMHCEnhanced expressionInhibitory functionAdaptive resistanceNovel inhibitory functionImmunotherapyPatientsContext-dependent mechanismsCellsDefining and Understanding Adaptive Resistance in Cancer Immunotherapy
Kim TK, Herbst RS, Chen L. Defining and Understanding Adaptive Resistance in Cancer Immunotherapy. Trends In Immunology 2018, 39: 624-631. PMID: 29802087, PMCID: PMC6066429, DOI: 10.1016/j.it.2018.05.001.Peer-Reviewed Original ResearchConceptsAnti-PD therapyLong-term survival benefitAvailable treatment regimensFraction of respondersSurvival benefitTumor immunityTumor-immune interactionsAdvanced cancerTreatment regimensCancer immunotherapyTumor regressionTherapyAccurate tissueSuch treatmentAdaptive resistancePatientsMolecular mechanismsTrue resistanceImmunotherapyRegimensRight targetCancerRespondersImmunityAppropriate interpretationB7-H1 maintains the polyclonal T cell response by protecting dendritic cells from cytotoxic T lymphocyte destruction
Chen L, Azuma T, Yu W, Zheng X, Luo L, Chen L. B7-H1 maintains the polyclonal T cell response by protecting dendritic cells from cytotoxic T lymphocyte destruction. Proceedings Of The National Academy Of Sciences Of The United States Of America 2018, 115: 3126-3131. PMID: 29507197, PMCID: PMC5866601, DOI: 10.1073/pnas.1722043115.Peer-Reviewed Original ResearchConceptsB7-H1 expressionDendritic cellsT cell responsesB7-H1CTL responsesTumor escapeB7-H1/PDCell responsesSubdominant T-cell responsesPolyclonal T cell responsesCombination cancer immunotherapyDifferent dendritic cellsAdaptive resistanceT lymphocyte destructionAdvanced human cancersMurine tumor modelsSurvival benefitTumor AgDominant AgAntibody blockadeCancer immunotherapyDC functionImmune destructionLymphocyte destructionT lymphocytes
2015
Downregulation of the Ubiquitin Ligase RNF125 Underlies Resistance of Melanoma Cells to BRAF Inhibitors via JAK1 Deregulation
Kim H, Frederick DT, Levesque MP, Cooper ZA, Feng Y, Krepler C, Brill L, Samuels Y, Hayward NK, Perlina A, Piris A, Zhang T, Halaban R, Herlyn MM, Brown KM, Wargo JA, Dummer R, Flaherty KT, Ronai Z. Downregulation of the Ubiquitin Ligase RNF125 Underlies Resistance of Melanoma Cells to BRAF Inhibitors via JAK1 Deregulation. Cell Reports 2015, 11: 1458-1473. PMID: 26027934, PMCID: PMC4681438, DOI: 10.1016/j.celrep.2015.04.049.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Line, TumorChromatography, LiquidDown-RegulationDrug Resistance, NeoplasmEnzyme InhibitorsFemaleHeterograftsHumansImmunoblottingImmunohistochemistryImmunoprecipitationJanus Kinase 1Mass SpectrometryMelanomaMiceMice, NudeProto-Oncogene Proteins B-rafRNA, Small InterferingTransfectionUbiquitin-Protein LigasesConceptsBRAF inhibitorsRTK expressionReceptor tyrosine kinasesRemarkable clinical responsesBRAFi-resistant melanomasInhibition of JAK1BRAFi-resistant tumorsClinical responseCombination therapyMost tumorsBRAF mutationsTumor specimensVivo xenograftsBRAFi resistanceMelanoma cellsElevated expressionMelanomaEGFRAdaptive resistanceTumorsRNF125MITF expressionTyrosine kinaseJAK1Downregulation
2009
MicroRNA dynamics in the stages of tumorigenesis correlate with hallmark capabilities of cancer
Olson P, Lu J, Zhang H, Shai A, Chun MG, Wang Y, Libutti SK, Nakakura EK, Golub TR, Hanahan D. MicroRNA dynamics in the stages of tumorigenesis correlate with hallmark capabilities of cancer. Genes & Development 2009, 23: 2152-2165. PMID: 19759263, PMCID: PMC2751988, DOI: 10.1101/gad.1820109.Peer-Reviewed Original ResearchConceptsPrimary tumorMouse modelHallmark capabilitiesPancreatic neuroendocrine tumorsAnti-angiogenic therapyTranscription factor ZEB1MiR changesMiR-200 familyMetastatic tumorsNeuroendocrine tumorsRare subsetEnhanced metastasisAngiogenesis inhibitorsMetastasisTumorsMiR signatureNeoplastic progressionHuman tumorsAltered expressionAdaptive resistanceExpression signaturesE-cadherinCancerMiRTherapy
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