grant
The role of stem-like CD8 T-cells in the abscopal response
NIHUS FederalResearch GrantFY2025AbscissionAbscopal effectAdjuvantBiometricsBiometryBiostatisticsCD11cCD8CD8 CellCD8 T cellsCD8 lymphocyteCD8+ T cellCD8+ T-LymphocyteCD8-Positive LymphocytesCD8-Positive T-LymphocytesCD8BCD8B1CD8B1 geneCancersClinicalClinical DataClinical ResearchClinical StudyClinical TrialsClinical Trials DesignCorynebacterium Diphtheriae ToxinDTR ProteinDendritic CellsDiagnosisDiphtheria ToxinDiphtheria Toxin SensitivityDistantEffector CellEnrollmentEvaluationExcisionExtirpationFlow CytofluorometriesFlow CytofluorometryFlow CytometryFlow MicrofluorimetryFlow MicrofluorometryFoundationsGene TranscriptionGenetic TranscriptionGoalsHB-EGF precursorITGAXITGAX geneImmunochemical ImmunologicImmunofluorescenceImmunofluorescence ImmunologicImmunologicImmunologicalImmunologicallyImmunologicsImpairmentInduction TherapyKnock-inLYT3Lymph Node Reticuloendothelial SystemLymph node properLymphatic nodesMalignant MelanomaMalignant NeoplasmsMalignant TumorMeasurementMediatingMediatorMelanomaMelanoma patientMethodsMiceMice MammalsMinorityModelingMurineMusNEOADJNeoadjuvantNeoadjuvant TherapyNeoadjuvant TreatmentNewly DiagnosedOutcomePD 1PD-1PD-1 antibodyPD1PD1 antibodyPatientsPeptide-MHCPeptide-Major Histocompatibility Protein ComplexPeptide/MHC ComplexPhenotypePilot ProjectsPreclinical dataPrimary NeoplasmPrimary TumorPrognosisProliferatingRNA ExpressionRNA SeqRNA sequencingRNAseqRadiationRadiation-Induced ChangeRandomizedRemovalRoleSamplingSortingStem Cell likeSurgical RemovalT cell infiltrationT cell responseT-Cell DepletionT-Cell SubsetsT-CellsT-LymphocyteT-Lymphocyte SubsetsT-cell depletion therapyT-lymphocyte depletion therapyT8 CellsT8 LymphocytesTestingTimeToxic effectToxicitiesTrainingTranscriptionTumor ImmunityUnresectableVeiled CellsaPD-1aPD1abscopal activityabscopal responseanti programmed cell death 1anti-PD-1anti-PD-1 Abanti-PD-1 antibodiesanti-PD-1 monoclonal antibodiesanti-PD1anti-PD1 Abanti-PD1 antibodiesanti-PD1 monoclonal antibodiesanti-canceranti-programmed cell death protein 1anti-programmed cell death protein 1 antibodiesanti-programmed death-1 antibodyanti-tumor immunityantiPD-1antigen-specific T cellsantitumor immunityarmcancer immunitycheck point blockadecheckpoint blockadecompare treatmentcostdiphtheria toxin receptordiptheria toxin receptordraining lymph nodeenrollexhaustexhaustionfirst in manfirst-in-humanflow cytophotometryhigh riskhuman studyimmune check point blockadeimmune checkpoint blockadeimmunostimulatory therapyimmunostimulatory treatmentimprovedimproved outcomeinduction therapiesinnovateinnovationinnovativeinsightirradiationknockinlymph glandlymph nodeslymphnodesmalignancymouse modelmurine modelneoplasm/cancernovelpMHCpatients suffering from melanomapatients with melanomapilot studypre-clinical studypreclinical findingspreclinical informationpreclinical studyprogenitor capacityprogenitor cell likeprogenitor-likeprogrammed cell death 1programmed cell death protein 1programmed death 1promoterpromotorrandomisationrandomizationrandomly assignedreceptor expressionregional lymph noderesectionresponsescRNA sequencingscRNA-seqsingle cell RNA-seqsingle cell RNAseqsingle cell expression profilingsingle cell transcriptomic profilingsingle-cell RNA sequencingsle2social rolestandard of carestem cell characteristicsstem-likestemnesssurvival outcomesynergismsystemic lupus erythematosus susceptibility 2thymus derived lymphocytetranscriptome sequencingtranscriptomic sequencingtreatment comparisontumorαPD-1αPD1
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PROJECT SUMMARY
Prognosis is poor for patients diagnosed with locally advanced melanoma. Survival outcomes are improved
with checkpoint blockade in the neoadjuvant, adjuvant and unresectable setting. Dual checkpoint blockade
further enhances outcomes, but often at the cost of significant clinical toxicity. Despite this progress, for the
more than…
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