grant
Interrogating Mechanisms of Anti-tumor Immunity in Human Subjects and Murine Models of IDH-Mutant Glioma Treated with All-Trans Retinoic Acid and PD-1 Inhibition
Organization UNIVERSITY OF PENNSYLVANIALocation PHILADELPHIA, UNITED STATESPosted 3 Jul 2023Deadline 30 Jun 2028
NIHUS FederalResearch GrantFY2025ATACATRAAbscissionAddressAdjuvantAgeAntibodiesBiological MarkersBloodBlood Reticuloendothelial SystemBody TissuesBrainBrain CancerBrain NeoplasiaBrain NeoplasmsBrain Nervous SystemBrain TumorsCD4 CellsCD4 Positive T LymphocytesCD4 T cellsCD4 helper T cellCD4 lymphocyteCD4+ T-LymphocyteCD4-Positive LymphocytesCD8CD8 CellCD8 T cellsCD8 lymphocyteCD8+ T cellCD8+ T-LymphocyteCD8-Positive LymphocytesCD8-Positive T-LymphocytesCD8BCD8B1CD8B1 geneCancersCell BodyCell Communication and SignalingCell SignalingCellsCessation of lifeCheckpoint inhibitorChemotherapy and RadiationChemotherapy and/or radiationClinicalClinical TrialsCombined Modality TherapyCytotoxic cellDNA mutationDataDeathDevelopmentDiffuseDisease remissionDoseEncephalonEpigeneticEpigenetic ChangeEpigenetic MechanismEpigenetic ProcessEvaluationExcisionExclusionExhibitsExpression SignatureExtirpationFutureGene Expression ProfileGene TranscriptionGenetic ChangeGenetic TranscriptionGenetic defectGenetic mutationGenotypeGlial Cell TumorsGlial NeoplasmGlial TumorGliomaGoalsHematologic CancerHematologic MalignanciesHematologic NeoplasmsHematological MalignanciesHematological NeoplasmsHematological TumorHematopoietic CancerHumanIFNIFN-GammaIFN-gIFN-γIFNGIFNγIRBIRBsImmuneImmune InterferonImmune MarkersImmune MonitoringImmune SurveillanceImmune checkpoint inhibitorImmune mediated therapyImmune systemImmunesImmunochemical ImmunologicImmunocompetentImmunologicImmunologic MarkersImmunologic MonitoringImmunologic SurveillanceImmunologicalImmunological MonitoringImmunologicallyImmunologically Directed TherapyImmunologicsImmunomonitoringImmunosuppressionImmunosuppression EffectImmunosuppressive EffectImmunosurveillanceImmunotherapeutic agentImmunotherapyInduction TherapyInfiltrationInflammatoryInstitutional Review BoardsInterferon GammaInterferon Type IIInterferonsIntracellular Communication and SignalingIsocitrate DehydrogenaseK lymphocyteKnowledgeLPTNLYT3Lymphatic cellLymphocyteLymphocyte FunctionLymphocyticLymphocytic InfiltrateMHC ReceptorMajor Histocompatibility Complex ReceptorMalignantMalignant - descriptorMalignant Hematologic NeoplasmMalignant NeoplasmsMalignant TumorMalignant Tumor of the BrainMalignant neoplasm of brainMediatingMediatorMiceMice MammalsModalityModelingModern ManMultimodal TherapyMultimodal TreatmentMurineMusMutationMyelogenousMyeloidMyeloid-derived suppressor cellsNEOADJNK CellsNatural Killer CellsNeoadjuvantNeoadjuvant TherapyNeoadjuvant TreatmentNeuroglial NeoplasmNeuroglial TumorOperative ProceduresOperative Surgical ProceduresOutputPD 1PD-1PD-1 inhibitorsPD1PD1 inhibitorsPathway interactionsPatientsPennsylvaniaPerformancePhase 2 Clinical TrialsPhase II Clinical TrialsPopulationPrediction of Response to TherapyRNA ExpressionRNA SeqRNA sequencingRNAseqRecurrenceRecurrentRegimenRegulatory T-LymphocyteRemissionRemovalReportingResearch SpecimenResistanceRetinoic AcidRetinoic Acid AgentRetinoic Acid and DerivativesRetinoidsSCM-1SCM-1aSCM1SCYC1SamplingSeriesSignal PathwaySignal TransductionSignal Transduction SystemsSignalingSleeping BeautySolidSpecificitySpecimenSurgicalSurgical InterventionsSurgical ProcedureSurgical RemovalT cell receptor repertoire sequencingT cell receptor sequencingT-Cell ActivationT-Cell Antigen ReceptorsT-Cell ReceptorT-CellsT-LymphocyteT-Lymphocyte and NK-CellT-Lymphocyte and Natural Killer CellT4 CellsT4 LymphocytesT8 CellsT8 LymphocytesTCR repertoire sequencingTCR sequencingTCR-seqTCRseqTechniquesTestingTherapeuticTherapeutically TargetableTissuesTrans Vitamin A AcidTranscriptionTregTretinoinTretinoinumTumor BiologyTumor CellTumor ImmunityTumor TissueTumor-Infiltrating LymphocytesUniversitiesValidationVitamin A AcidXCL1XCL1 geneactivate T cellsadult youthagesall-trans-Retinoic Acidall-trans-Vitamin A acidanti programmed cell death protein 1 inhibitoranti-PD-1 inhibitorsanti-PD1 inhibitorsanti-tumor immunityantitumor immunitybio-markersbiologic markerbiological signal transductionbiomarkercancer immunitycell typecheck point blockadecheck point inhibitioncheckpoint blockadecheckpoint inhibitionchemo/radiation therapychemotherapy and radiotherapyclinical efficacycohortcombination therapycombined modality treatmentcombined treatmentdesigndesigningdevelopmentalepigenetic gene silencingepigenetic silencingepigeneticallyexhaustionexperimentexperimental researchexperimental studyexperimentsgene expression patterngene expression signaturegene networkgene signaturesgenetic signaturegenome mutationglial-derived tumorhuman subjectimmune check point blockadeimmune check point inhibitionimmune check point inhibitorimmune checkpoint blockadeimmune checkpoint inhibitionimmune competentimmune drugsimmune suppressionimmune suppressive activityimmune suppressive functionimmune therapeutic approachimmune therapeutic interventionsimmune therapeutic regimensimmune therapeutic strategyimmune therapyimmune-based biomarkersimmune-based therapeuticsimmune-based therapiesimmune-based treatmentsimmuno therapyimmunogenicimmunogenicityimmunologic therapeuticsimmunological biomarkersimmunological markersimmunosuppressive activityimmunosuppressive functionimmunosuppressive myeloid cellsimmunosuppressive responseimmunotherapeuticsimmunotherapy agentinduction therapieslFN-Gammalymph cellmalignancymouse modelmulti-modal therapymulti-modal treatmentmurine modelmutantmyeloid suppressor cellsmyeloid-derived suppressive cellsneoplasm/cancerneoplastic cellneuroglia neoplasmneuroglia tumorpathwayphase II protocolpre-clinicalpreclinicalpredict responsivenesspredict therapeutic responsepredict therapy responsepredicting responseprogrammed cell death 1programmed cell death protein 1programmed death 1radiation or chemotherapyregulatory T-cellsresectionresistantresponseresponse to therapyresponse to treatmentrestorationscRNA sequencingscRNA-seqsingle cell RNA-seqsingle cell RNAseqsingle cell expression profilingsingle cell transcriptomic profilingsingle-cell RNA sequencingsle2small moleculespecific biomarkerssuppressive myeloid cellssurgerysystemic lupus erythematosus susceptibility 2therapeutic responsetherapy predictiontherapy responsethymus derived lymphocytetrans-Retinoic Acidtranscriptional profiletranscriptional signaturetranscriptome sequencingtranscriptomic sequencingtreatment predictiontreatment responsetreatment response predictiontreatment responsivenesstumortumor eradicationtumors in the brainvalidationsyoung adultyoung adult ageyoung adulthood
Description preview
Project Abstract
Diffuse gliomas are fatal brain tumors that respond poorly to current immunotherapies. Using
both mice models and human clinical trial data, we propose a series of experiments to identify
immune biomarkers and key immune cell types that predict tumor responsiveness to therapy.
These results will further our understanding of brain…
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