2024
KLF13 promotes SLE pathogenesis by modifying chromatin accessibility of key proinflammatory cytokine genes
Wang A, Fairhurst A, Liu K, Wakeland B, Barnes S, Malladi V, Viswanathan K, Arana C, Dozmorov I, Singhar A, Du Y, Imam M, Moses A, Chen C, Sunkavalli A, Casco J, Rakheja D, Li Q, Mohan C, Clayberger C, Wakeland E, Khan S. KLF13 promotes SLE pathogenesis by modifying chromatin accessibility of key proinflammatory cytokine genes. Communications Biology 2024, 7: 1446. PMID: 39506084, PMCID: PMC11541912, DOI: 10.1038/s42003-024-07099-0.Peer-Reviewed Original ResearchConceptsSystemic lupus erythematosusMyeloid cellsLupus nephritisT cellsKidneys of lupus-prone miceSystemic lupus erythematosus pathogenesisLevels of proinflammatory cytokinesLupus-prone miceActivated myeloid cellsActivated T cellsT cell activationProduction of RANTEST cell hyperactivityProinflammatory cytokine genesAssociated with increased productionLupus pathogenesisProinflammatory cytokines/chemokinesSle1 locusLupus erythematosusImmune activationProinflammatory cytokinesCytokine signaling pathwaysCytokine genesGenome-wide transcriptional changesReceptor ligandsZinc finger nuclease-mediated gene editing in hematopoietic stem cells results in reactivation of fetal hemoglobin in sickle cell disease
Lessard S, Rimmelé P, Ling H, Moran K, Vieira B, Lin Y, Rajani G, Hong V, Reik A, Boismenu R, Hsu B, Chen M, Cockroft B, Uchida N, Tisdale J, Alavi A, Krishnamurti L, Abedi M, Galeon I, Reiner D, Wang L, Ramezi A, Rendo P, Walters M, Levasseur D, Peters R, Harris T, Hicks A. Zinc finger nuclease-mediated gene editing in hematopoietic stem cells results in reactivation of fetal hemoglobin in sickle cell disease. Scientific Reports 2024, 14: 24298. PMID: 39414860, PMCID: PMC11484757, DOI: 10.1038/s41598-024-74716-7.Peer-Reviewed Original ResearchConceptsHematopoietic stem cellsSickle cell diseaseTreatment of sickle cell diseaseFetal hemoglobinCell therapyReactivation of fetal hemoglobinCell diseaseMonths of follow-upStem cellsReactivate fetal hemoglobinResults of preclinical studiesPotential treatmentEngraftment in vivoAutologous cell therapyNovel cell therapiesVaso-occlusive crisisIncreased total hemoglobinErythroid progenyHealthy donorsPreclinical studiesClinical developmentFollow-upErythroid enhancerBCL11A erythroid enhancerGATAA motifsDeep sequencing of candidate genes identified 14 variants associated with smoking abstinence in an ethnically diverse sample
Cinciripini P, Wetter D, Wang J, Yu R, Kypriotakis G, Kumar T, Robinson J, Cui Y, Green C, Bergen A, Kosten T, Scherer S, Shete S. Deep sequencing of candidate genes identified 14 variants associated with smoking abstinence in an ethnically diverse sample. Scientific Reports 2024, 14: 6385. PMID: 38493193, PMCID: PMC10944542, DOI: 10.1038/s41598-024-56750-7.Peer-Reviewed Original ResearchMeSH KeywordsBupropionForkhead Transcription FactorsHigh-Throughput Nucleotide SequencingHumansNicotinic AgonistsRepressor ProteinsSmokingSmoking CessationConceptsIdentification of novel lociSequencing of candidate genesRare variant associationsMapped to genesReceptor signaling pathwayNovel lociGenes associated with regulationVariant associationsCandidate genesProtective lociDeep sequencingRegulation of bodyweightGenetic studiesCanonical pathwaysSignaling pathwayRare variantsGenetic profileTarget of pharmacotherapyTumor suppressionAssociated with cancerGenesPublic health tollRandomized controlled trialsSubstance use disordersEthnically diverse sample
2023
Primary complex motor stereotypies are associated with de novo damaging DNA coding mutations that identify KDM5B as a risk gene
Fernandez T, Williams Z, Kline T, Rajendran S, Augustine F, Wright N, Sullivan C, Olfson E, Abdallah S, Liu W, Hoffman E, Gupta A, Singer H. Primary complex motor stereotypies are associated with de novo damaging DNA coding mutations that identify KDM5B as a risk gene. PLOS ONE 2023, 18: e0291978. PMID: 37788244, PMCID: PMC10547198, DOI: 10.1371/journal.pone.0291978.Peer-Reviewed Original ResearchConceptsRisk genesDe novo damaging variantsGene expression patternsWhole-exome DNA sequencingMid-fetal developmentAdditional risk genesHigh-confidence risk genesParent-child triosGene OntologyCell signalingExpression patternsCalcium ion transportFunctional convergenceCell cycleDamaging variantsGenesDNA sequencingDe novoASD probandsGenetic etiologyBiological mechanismsSequencingDNANetwork analysisIon transportDifferential Impact of SPOP Mutation in Prostate and Endometrial Cancers
Gebrael G, Zengin Z, Swami U. Differential Impact of SPOP Mutation in Prostate and Endometrial Cancers. JCO Precision Oncology 2023, 7: e2300397. PMID: 37972335, DOI: 10.1200/po.23.00397.Peer-Reviewed Original ResearchSolitary Fibrous Tumor of the Pancreas
Yavas A, Tan J, Ozkan H, Yilmaz F, Reid M, Bagci P, Shi J, Shia J, Adsay V, Klimstra D, Basturk O. Solitary Fibrous Tumor of the Pancreas. The American Journal Of Surgical Pathology 2023, 47: 1230-1242. PMID: 37573546, PMCID: PMC10592360, DOI: 10.1097/pas.0000000000002108.Peer-Reviewed Original ResearchConceptsPancreatic solitary fibrous tumorSolitary fibrous tumorNuclear STAT6 expressionFibrous tumorTumor cellsDifferential diagnosis of mesenchymal neoplasmsSTAT6 expressionAtypical spindle cell tumorDiagnosis of mesenchymal neoplasmsLow-grade stromal tumorsMetastatic renal cell carcinomaSpindle tumor cellsFree of diseaseLow-grade sarcomaSpindle cell tumorsRenal cell carcinomaNAB2-STAT6 fusionFollow-up dataStromal tumorsHypervascular massNeuroendocrine tumorsCell carcinomaMesenchymal neoplasmsCell tumorsCystic areasCytomorphologic, immunophenotypical and molecular features of pancreatic acinar cell carcinoma
Sun T, Gilani S, Jain D, Cai G. Cytomorphologic, immunophenotypical and molecular features of pancreatic acinar cell carcinoma. Diagnostic Cytopathology 2023, 51: 674-683. PMID: 37469257, DOI: 10.1002/dc.25196.Peer-Reviewed Original ResearchMeSH KeywordsCarcinoma, Acinar CellCarcinoma, Pancreatic DuctalHumansPancreasPancreatic NeoplasmsRepressor ProteinsConceptsPancreatic acinar cell carcinomaPancreatic ductal carcinomaAcinar cell carcinomaCell carcinomaMixed acinar-ductal carcinomaMixed acinar-neuroendocrine carcinomaMolecular featuresComprehensive molecular profilingDifferent molecular alterationsDistinct molecular featuresImmunophenotypical featuresNeuroendocrine featuresDuctal carcinomaRare tumorCCDC6-RETCytohistological correlationKi-67Large cohortCytologic diagnosisBiomarker assessmentCytology featuresCytology specimensCarcinomaMolecular alterationsGermline mutations
2022
Regulatory enhancer profiling of mesenchymal-type gastric cancer reveals subtype-specific epigenomic landscapes and targetable vulnerabilities
Ho S, Sheng T, Xing M, Ooi W, Xu C, Sundar R, Huang K, Li Z, Kumar V, Ramnarayanan K, Zhu F, Srivastava S, Bin Adam Isa Z, Anene-Nzelu C, Razavi-Mohseni M, Shigaki D, Ma H, Tan A, Ong X, Lee M, Tay S, Guo Y, Huang W, Li S, Beer M, Foo R, Teh M, Skanderup A, Teh B, Tan P. Regulatory enhancer profiling of mesenchymal-type gastric cancer reveals subtype-specific epigenomic landscapes and targetable vulnerabilities. Gut 2022, 72: 226-241. PMID: 35817555, DOI: 10.1136/gutjnl-2021-326483.Peer-Reviewed Original ResearchConceptsEpigenomic landscapeGastric cancerEnhancer landscapeGenome-wide epigenomic profilesDownstream targetsPharmacological inhibitionCell linesClinically aggressive subtypeTargetable genomic alterationsMultiple molecular subtypesChIP-seqPoor patient survivalGenomic associationsGC cell linesTranscriptomic scenarioEpigenomic profilingSuper-enhancersChromatin immunoprecipitationRNA sequencingTranscriptome profilingUpstream regulatorGenomic alterationsTherapy resistanceCRISPR/Cas9 editingPatient survivalEvaluation of TRPS1 Expression in Pleural Effusion Cytology Specimens With Metastatic Breast Carcinoma
Wang M, Stendahl K, Cai G, Adeniran A, Harigopal M, Gilani SM. Evaluation of TRPS1 Expression in Pleural Effusion Cytology Specimens With Metastatic Breast Carcinoma. American Journal Of Clinical Pathology 2022, 158: 416-425. PMID: 35760555, DOI: 10.1093/ajcp/aqac066.Peer-Reviewed Original ResearchConceptsTrichorhinophalangeal syndrome type 1Breast originMetastatic carcinomaTRPS1 expressionBreast primaryBreast carcinomaPrimary siteMC casesMetastatic breast carcinomaSquamous cell carcinomaPleural effusion cytologySyndrome type 1Cell block materialStrong nuclear expressionEffusion cytology specimensCell carcinomaUrothelial carcinomaIHC panelMalignant melanomaLung adenocarcinomaIHC stainingPositive stainingCytology specimensCarcinomaEffusion cytologyPOU2F3 in SCLC: Clinicopathologic and Genomic Analysis With a Focus on Its Diagnostic Utility in Neuroendocrine-Low SCLC
Baine MK, Febres-Aldana CA, Chang JC, Jungbluth AA, Sethi S, Antonescu CR, Travis WD, Hsieh MS, Roh MS, Homer RJ, Ladanyi M, Egger JV, Lai WV, Rudin CM, Rekhtman N. POU2F3 in SCLC: Clinicopathologic and Genomic Analysis With a Focus on Its Diagnostic Utility in Neuroendocrine-Low SCLC. Journal Of Thoracic Oncology 2022, 17: 1109-1121. PMID: 35760287, PMCID: PMC9427708, DOI: 10.1016/j.jtho.2022.06.004.Peer-Reviewed Original ResearchConceptsNeuroendocrine markersDiagnostic utilityLarge cell neuroendocrine carcinomaDiagnosis of SCLCSquamous cell carcinomaCell neuroendocrine carcinomaLung cancer typesMajor lung cancer typesNeuroendocrine marker expressionLung carcinoma subtypesWarrants further studyDistinct genomic alterationsClinical characteristicsCell carcinomaNeuroendocrine carcinomaLung tumorsCarcinoma subtypesLarge cohortDiagnostic mimicsTP53 alterationsMYC amplificationRecent markersTherapeutic targetingTuft cellsChallenging subsetLCOR mediates interferon-independent tumor immunogenicity and responsiveness to immune-checkpoint blockade in triple-negative breast cancer
Pérez-Núñez I, Rozalén C, Palomeque JÁ, Sangrador I, Dalmau M, Comerma L, Hernández-Prat A, Casadevall D, Menendez S, Liu DD, Shen M, Berenguer J, Ruiz IR, Peña R, Montañés JC, Albà MM, Bonnin S, Ponomarenko J, Gomis RR, Cejalvo JM, Servitja S, Marzese DM, Morey L, Voorwerk L, Arribas J, Bermejo B, Kok M, Pusztai L, Kang Y, Albanell J, Celià-Terrassa T. LCOR mediates interferon-independent tumor immunogenicity and responsiveness to immune-checkpoint blockade in triple-negative breast cancer. Nature Cancer 2022, 3: 355-370. PMID: 35301507, DOI: 10.1038/s43018-022-00339-4.Peer-Reviewed Original ResearchMeSH KeywordsHumansImmune Checkpoint InhibitorsImmunotherapyInterferonsMelanomaRepressor ProteinsSkin NeoplasmsTriple Negative Breast NeoplasmsConceptsTriple-negative breast cancerCancer stem cellsLigand-dependent corepressorTumor immunogenicityBreast cancerImmune checkpoint blockadeBreast cancer metastasisICB efficacyICB resistanceLCoR expressionClinical responsePresentation machineryImmune escapeAPM genesPreclinical modelsTherapy resistanceCancer metastasisPromising targetOvercame resistanceIFNRNA therapyCancerImmunogenicitySignaling-independent mannerStem cellsOverview of the 2022 WHO Classification of Neuroendocrine Neoplasms
Rindi G, Mete O, Uccella S, Basturk O, La Rosa S, Brosens L, Ezzat S, de Herder W, Klimstra D, Papotti M, Asa S. Overview of the 2022 WHO Classification of Neuroendocrine Neoplasms. Endocrine Pathology 2022, 33: 115-154. PMID: 35294740, DOI: 10.1007/s12022-022-09708-2.Peer-Reviewed Original ResearchMeSH KeywordsCarcinoma, NeuroendocrineHumansImmunohistochemistryNeuroendocrine TumorsReceptors, SomatostatinRepressor ProteinsWorld Health OrganizationConceptsNeuroendocrine tumorsNeuroendocrine neoplasmsSomatostatin receptorsWHO classificationNon-neuroendocrineDifferential diagnosisWHO Classification of EndocrineExpression of somatostatin receptorsWHO classification of neuroendocrine neoplasmsG3 neuroendocrine tumorsAssociated with germline mutationsPancreatic neuroendocrine tumorsClassification of neuroendocrine neoplasmsEctopic hormone productionLoss of RbLoss of ATRXSite of originComposite tumorMetastatic lesionsAberrant p53Amphicrine tumorsEpithelial neoplasmsPrecursor lesionsTheranostic biomarkersGermline mutationsPseudohypoxic HIF pathway activation dysregulates collagen structure-function in human lung fibrosis
Brereton CJ, Yao L, Davies ER, Zhou Y, Vukmirovic M, Bell JA, Wang S, Ridley RA, Dean L, Andriotis OG, Conforti F, Brewitz L, Mohammed S, Wallis T, Tavassoli A, Ewing RM, Alzetani A, Marshall BG, Fletcher SV, Thurner PJ, Fabre A, Kaminski N, Richeldi L, Bhaskar A, Schofield CJ, Loxham M, Davies DE, Wang Y, Jones MG. Pseudohypoxic HIF pathway activation dysregulates collagen structure-function in human lung fibrosis. ELife 2022, 11: e69348. PMID: 35188460, PMCID: PMC8860444, DOI: 10.7554/elife.69348.Peer-Reviewed Original ResearchConceptsHIF pathway activationPathway activationLung fibrosisOxidative stressHuman lung fibrosisOxidative stress scoreFibrillar collagen synthesisHypoxia-inducible factor (HIF) pathway activationExtracellular matrixActive fibrogenesisFibrosisHuman fibrosisFibrosis tissueHIF activationStress scoresVivo studiesCollagen synthesisMesenchymal cellsCritical pathwaysDownstream activationNormal fibroblastsCritical regulatorHIFActivationHuman tissuesPrdm6 controls heart development by regulating neural crest cell differentiation and migration
Hong L, Li N, Gasque V, Mehta S, Ye L, Wu Y, Li J, Gewies A, Ruland J, Hirschi KK, Eichmann A, Hendry C, van Dijk D, Mani A. Prdm6 controls heart development by regulating neural crest cell differentiation and migration. JCI Insight 2022, 7: e156046. PMID: 35108221, PMCID: PMC8876496, DOI: 10.1172/jci.insight.156046.Peer-Reviewed Original ResearchConceptsCardiac NCCNeural crest cell fateNeural crest cell differentiationSingle-cell RNA-seq analysisRNA-seq analysisDorsal neural tubeG1-S progressionFate-mapping approachCNCC migrationSpecification genesH4K20 monomethylationCell fateTranscriptomic analysisEpigenetic modifiersHeart developmentRegulated networkTranscript levelsKey regulatorMolecular mechanismsCell differentiationNeural tubePRDM6Ductus arteriosusPotential targetDifferentiation
2021
1-deoxysphingolipids bind to COUP-TF to modulate lymphatic and cardiac cell development
Wang T, Wang Z, de Fabritus L, Tao J, Saied EM, Lee HJ, Ramazanov BR, Jackson B, Burkhardt D, Parker M, Gleinich AS, Wang Z, Seo DE, Zhou T, Xu S, Alecu I, Azadi P, Arenz C, Hornemann T, Krishnaswamy S, van de Pavert SA, Kaech SM, Ivanova NB, Santori FR. 1-deoxysphingolipids bind to COUP-TF to modulate lymphatic and cardiac cell development. Developmental Cell 2021, 56: 3128-3145.e15. PMID: 34762852, PMCID: PMC8628544, DOI: 10.1016/j.devcel.2021.10.018.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell DifferentiationGene Expression RegulationHumansLymphatic VesselsMiceOrganogenesisRepressor ProteinsSphingolipidsConceptsLigand-binding domainNuclear hormone receptor activityTranscriptional networksCellular physiologyCOUP-TFDifferentiation programCell-based assaysHormone receptor activityTranscriptional activityMetabolic enzymesCell developmentPhysiological regulatorPhysiological modulatorBindsPhysiological concentrationsReceptor activityLymphatic vesselsTranscriptionNervous systemNR2F1RegulatorPhenocopiesModulatorEnzymePhysiologyKDM5B promotes immune evasion by recruiting SETDB1 to silence retroelements
Zhang SM, Cai WL, Liu X, Thakral D, Luo J, Chan LH, McGeary MK, Song E, Blenman KRM, Micevic G, Jessel S, Zhang Y, Yin M, Booth CJ, Jilaveanu LB, Damsky W, Sznol M, Kluger HM, Iwasaki A, Bosenberg MW, Yan Q. KDM5B promotes immune evasion by recruiting SETDB1 to silence retroelements. Nature 2021, 598: 682-687. PMID: 34671158, PMCID: PMC8555464, DOI: 10.1038/s41586-021-03994-2.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Line, TumorDNA-Binding ProteinsEpigenesis, GeneticGene SilencingHeterochromatinHistone-Lysine N-MethyltransferaseHumansInterferon Type IJumonji Domain-Containing Histone DemethylasesMaleMelanomaMiceMice, Inbred C57BLMice, KnockoutNuclear ProteinsRepressor ProteinsRetroelementsTumor EscapeConceptsImmune checkpoint blockadeImmune evasionCheckpoint blockadeImmune responseAnti-tumor immune responseRobust adaptive immune responseTumor immune evasionAnti-tumor immunityAdaptive immune responsesType I interferon responseDNA-sensing pathwayMouse melanoma modelImmunotherapy resistanceMost patientsCurrent immunotherapiesTumor immunogenicityImmune memoryMelanoma modelCytosolic RNA sensingRole of KDM5BConsiderable efficacyInterferon responseImmunotherapyEpigenetic therapyBlockadeTargeting the Atf7ip–Setdb1 Complex Augments Antitumor Immunity by Boosting Tumor Immunogenicity
Hu H, Khodadadi-Jamayran A, Dolgalev I, Cho H, Badri S, Chiriboga LA, Zeck B, De Rodas Gregorio M, Dowling CM, Labbe K, Deng J, Chen T, Zhang H, Zappile P, Chen Z, Ueberheide B, Karatza A, Han H, Ranieri M, Tang S, Jour G, Osman I, Sucker A, Schadendorf D, Tsirigos A, Schalper KA, Velcheti V, Huang HY, Jin Y, Ji H, Poirier JT, Li F, Wong KK. Targeting the Atf7ip–Setdb1 Complex Augments Antitumor Immunity by Boosting Tumor Immunogenicity. Cancer Immunology Research 2021, 9: 1298-1315. PMID: 34462284, PMCID: PMC9414288, DOI: 10.1158/2326-6066.cir-21-0543.Peer-Reviewed Original ResearchConceptsHistone lysine methyltransferase 1Common adaptive mechanismSuppressor screenChromatin modifiersIntron retentionSET domainEpigenetic regulatorsEpigenetic modificationsEpigenetic modifiersType I interferon responseMethyltransferase 1I interferon responseHuman cancersTranscription factor 7Immune invasionInterferon responseAdaptive mechanismsFactor 7GenesCritical roleExpressionImmune evasionRejection of cellsAntigen processingAntigen expressionMethylation of dual-specificity phosphatase 4 controls cell differentiation
Su H, Jiang M, Senevirathne C, Aluri S, Zhang T, Guo H, Xavier-Ferrucio J, Jin S, Tran NT, Liu SM, Sun CW, Zhu Y, Zhao Q, Chen Y, Cable L, Shen Y, Liu J, Qu CK, Han X, Klug CA, Bhatia R, Chen Y, Nimer SD, Zheng YG, Iancu-Rubin C, Jin J, Deng H, Krause DS, Xiang J, Verma A, Luo M, Zhao X. Methylation of dual-specificity phosphatase 4 controls cell differentiation. Cell Reports 2021, 36: 109421. PMID: 34320342, PMCID: PMC9110119, DOI: 10.1016/j.celrep.2021.109421.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsArginineCell DifferentiationCell LineChildDual-Specificity PhosphatasesEnzyme StabilityFemaleHEK293 CellsHumansMaleMAP Kinase Signaling SystemMegakaryocytesMethylationMice, Inbred C57BLMiddle AgedMitogen-Activated Protein Kinase PhosphatasesMyelodysplastic Syndromesp38 Mitogen-Activated Protein KinasesPolyubiquitinProtein-Arginine N-MethyltransferasesProteolysisRepressor ProteinsUbiquitinationYoung AdultConceptsDual-specificity phosphataseCell differentiationSingle-cell transcriptional analysisP38 MAPKControls cell differentiationE3 ligase HUWE1Knockdown screeningMK differentiationTranscriptional analysisMegakaryocyte differentiationProtein kinaseP38 axisP38 activationPRMT1Transcriptional signatureContext of thrombocytopeniaMK cellsMechanistic insightsPharmacological inhibitionDifferentiationMethylationMAPKPhosphataseUbiquitinylationActivationProtein neddylation as a therapeutic target in pulmonary and extrapulmonary small cell carcinomas
Norton J, Augert A, Eastwood E, Basom R, Rudin C, MacPherson D. Protein neddylation as a therapeutic target in pulmonary and extrapulmonary small cell carcinomas. Genes & Development 2021, 35: 870-887. PMID: 34016692, PMCID: PMC8168556, DOI: 10.1101/gad.348316.121.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBasic Helix-Loop-Helix Transcription FactorsCarcinoma, Small CellCell DeathCell Line, TumorCOP9 Signalosome ComplexCyclopentanesDisease Models, AnimalGene Expression Regulation, NeoplasticHeterograftsHumansLung NeoplasmsMiceNEDD8 ProteinNeuroendocrine CellsProteinsPyrimidinesRepressor ProteinsSequence DeletionConceptsSmall cell lung carcinomaSmall cell carcinomaExtrapulmonary small cell carcinomaNeddylation inhibitionCell carcinomaCell statesGenome-scale CRISPR/Therapeutic targetPatient-derived xenograft modelsCell linesDeletion of componentsSolid tumor malignanciesCell lung carcinomaNovel therapeutic approachesPotential therapeutic targetSuppressor screenSCLC cell linesCOP9 signalosomeProtein neddylationCRISPR/Genetic suppressionPathway genesPDX modelsMajor regulatorLung carcinomaTargeting resistance to radiation-immunotherapy in cold HNSCCs by modulating the Treg-dendritic cell axis
Knitz MW, Bickett TE, Darragh LB, Oweida AJ, Bhatia S, Van Court B, Bhuvane S, Piper M, Gadwa J, Mueller AC, Nguyen D, Nangia V, Osborne DG, Bai X, Ferrara SE, Boss MK, Goodspeed A, Burchill MA, Tamburini BAJ, Chan ED, Pickering CR, Clambey ET, Karam SD. Targeting resistance to radiation-immunotherapy in cold HNSCCs by modulating the Treg-dendritic cell axis. Journal For ImmunoTherapy Of Cancer 2021, 9: e001955. PMID: 33883256, PMCID: PMC8061827, DOI: 10.1136/jitc-2020-001955.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic Agents, ImmunologicalBasic-Leucine Zipper Transcription FactorsCell Line, TumorCombined Modality TherapyDendritic CellsDrug Resistance, NeoplasmHead and Neck NeoplasmsImmune Checkpoint InhibitorsImmunotherapyInterleukin-2 Receptor alpha SubunitLymphocyte DepletionMice, Inbred BALB CMice, Inbred C57BLMice, KnockoutPhenotypeRadiation Dose HypofractionationRadiation ToleranceRepressor ProteinsSquamous Cell Carcinoma of Head and NeckT-Lymphocytes, RegulatoryTumor BurdenTumor MicroenvironmentTumor Necrosis Factor Receptor Superfamily, Member 9ConceptsCombination radiation therapyRadiation therapyDendritic cellsLymph nodesMouse modelRadioresistant tumorsRegulatory T-cell depletionT cell effector responsesTumor-draining lymph nodesNeck squamous cell carcinomaOral squamous cell carcinoma tumorsT cell-dependent responsesSquamous cell carcinoma tumorsAnti-CD137 treatmentDC activation statusGy x 5Higher Treg numbersPlasticity of TregsAdoptive transfer studiesT-cell depletionSquamous cell carcinomaCell-dependent responsesOrthotopic mouse modelTumor necrosis factorαNew therapeutic opportunities
This site is protected by hCaptcha and its Privacy Policy and Terms of Service apply