grant
Interrogating Mechanisms of Suppressed Tpex Immunotherapy Response in Metastatic Tumor-Draining Lymph Nodes
Organization UNIVERSITY OF CALIFORNIA, SAN FRANCISCOLocation SAN FRANCISCO, UNITED STATESPosted 1 Sept 2025Deadline 31 Aug 2028
NIHUS FederalResearch GrantFY2025Activities of Daily LivingActivities of everyday lifeAddressAffectAntigensBiologicalBiologyBloodBlood Reticuloendothelial SystemCD4 CellsCD4 Positive T LymphocytesCD4 T cellsCD4 helper T cellCD4 lymphocyteCD4+ T-LymphocyteCD4-Positive LymphocytesCD8 CellCD8 T cellsCD8 lymphocyteCD8+ T cellCD8+ T-LymphocyteCD8-Positive LymphocytesCD8-Positive T-LymphocytesCaliforniaCancersCell BodyCell CommunicationCell Communication and SignalingCell InteractionCell SignalingCell-Mediated Lympholytic CellsCell-to-Cell InteractionCellsCo-cultureCocultivationCocultureCoculture TechniquesCytolytic T-CellCytometryCytotoxic T CellCytotoxic T-LymphocytesDataDefectDendritic CellsDendritic cell activationDevelopment and ResearchDiseaseDisorderDisseminated Malignant NeoplasmEnvironmentEpigeneticEpigenetic ChangeEpigenetic MechanismEpigenetic ProcessFellowshipFrequenciesFundingGeneticHNC patientHNSCCHead and Neck CancerHead and Neck CarcinomaHead and Neck Lymph NodeHead and Neck Squamous Cell CarcinomaImmuneImmune Cell ActivationImmune mediated therapyImmune responseImmunesImmunologically Directed TherapyImmunologistImmunologyImmunosuppressionImmunosuppression EffectImmunosuppressive EffectImmunotherapyImpairmentIn VitroIndividualInstitutionInterruptionIntracellular Communication and SignalingKineticsLaboratoriesLymph Node Reticuloendothelial SystemLymph Node of Head, Face and NeckLymph node properLymphatic cellLymphatic nodesLymphocyteLymphocyticMHC ReceptorMajor Histocompatibility Complex ReceptorMalignant CellMalignant Head and Neck NeoplasmMalignant NeoplasmsMalignant TumorMeasuresMediatorMentorshipMetastasisMetastasis to Lymph NodesMetastasizeMetastatic CancerMetastatic LesionMetastatic Malignant NeoplasmMetastatic MassMetastatic NeoplasmMetastatic Neoplasm to Lymph NodesMetastatic TumorMetastatic Tumor to Lymph NodesMethodsMiceMice MammalsModelingMurineMusNeoplasm MetastasisNon-metastaticNonmetastaticOralPD-L1 antibodyPD-L1 therapyPD-L1 treatmentPDL1 therapyPDL1 treatmentPatientsPeripheralPhenotypePlayProductivityPropertyProteomicsPublishingR & DR&DR-Series Research ProjectsR01 MechanismR01 ProgramReceptor SignalingRecurrenceRecurrentRegulationRegulatory T-LymphocyteResearchResearch GrantsResearch Project GrantsResearch ProjectsResectedRoleSCCHNSan FranciscoScientistSecondary NeoplasmSecondary TumorSideSignal TransductionSignal Transduction SystemsSignalingStem Cell likeSystemT cell based immune therapyT cell based therapeuticsT cell based therapyT cell directed therapiesT cell immune therapyT cell immunotherapyT cell responseT cell targeted therapeuticsT cell therapyT cell treatmentT cell-based immunotherapyT cell-based treatmentT cellular immunotherapyT cellular therapyT lymphocyte based immunotherapyT lymphocyte based therapyT lymphocyte therapeuticT lymphocyte treatmentT-Cell Antigen ReceptorsT-Cell DevelopmentT-Cell OntogenyT-Cell ReceptorT-CellsT-LymphocyteT-Lymphocyte DevelopmentT-cell therapeuticsT-cell transfer therapyT4 CellsT4 LymphocytesT8 CellsT8 LymphocytesTestingTrainingTregTumor BurdenTumor ImmunityTumor LoadTumor-Infiltrating LymphocytesTumor-infiltrating immune cellsUniversitiesVeiled CellsWorkaPD-L1aPD-L1 antibodiesaPD-L1 therapyaPD-L1 treatmentadoptive T cell transferadoptive T lymphocyte transferadoptive T-cell therapyanti programmed cell death ligand 1anti programmed cell death ligand 1 therapyanti programmed cell death ligand 1 treatmentanti programmed cell death protein ligand 1anti programmed cell death protein ligand 1 therapyanti programmed cell death protein ligand 1 treatmentanti-PD-(L)1anti-PD-L1anti-PD-L1 antibodiesanti-PD-L1 monoclonal antibodiesanti-PD-L1 therapyanti-PD-L1 treatmentanti-PDL-1anti-PDL1anti-PDL1 antibodiesanti-PDL1 therapyanti-PDL1 treatmentanti-cancer immunotherapyanti-tumor immune responseanti-tumor immunityantiPD-L1anticancer immunotherapyantitumor immunitybiologicbiological signal transductioncancer cellcancer immunitycancer immunotherapycancer metastasiscancer microenvironmentcancer typecareercell mediated immune responsecheck point blockadecheckpoint blockadeclinical relevanceclinically relevantcytotoxicdaily living functiondaily living functionalitydraining lymph nodeepigeneticallyexhaustexhaustionfunctional abilityfunctional capacityhead and neck cancer patienthead and neck squamous carcinomahead and neck squamous cell cancerhead/neck cancerhigh dimensionalityhost responseimmune activationimmune cell infiltration of tumorsimmune cells infiltrating the tumorimmune cells that infiltrate the tumorimmune check point blockadeimmune checkpoint blockadeimmune suppressionimmune suppressive activityimmune suppressive functionimmune system responseimmune therapeutic approachimmune therapeutic interventionsimmune therapeutic regimensimmune therapeutic strategyimmune therapyimmune-based cancer therapiesimmune-based therapiesimmune-based treatmentsimmuno therapyimmunogenimmunoresponseimmunosuppressive activityimmunosuppressive functionimmunosuppressive responseimmunotherapy for cancerimmunotherapy of cancerin vitro Modelin vivoinfiltration of tumors by immune cellsinsightintratumoral immune cellintratumoral immune infiltratekiller T celllymph celllymph glandlymph node metastasislymph nodeslymphnodeslymphocyte traffickingmalignancymalignant head and neck tumormigrationmouse modelmurine modelneoplasm/cancernew approachesnew therapeutic approachnew therapeutic interventionnew therapeutic strategiesnew therapy approachesnew treatment approachnew treatment strategynovelnovel approachesnovel strategiesnovel strategynovel therapeutic approachnovel therapeutic interventionnovel therapeutic strategiesnovel therapy approachperipheral bloodpharmacologicpolarized cellpreventpreventingprogenitorprogenitor capacityprogenitor cell likeprogenitor-likeregional lymph noderegulatory T-cellsresearch and developmentresponsesingle cell analysisskillssocial rolestem cell characteristicsstem-likestemnesstherapeutic T-cell platformtherapeutic targetthymus derived lymphocytetooltranscriptomicstumortumor cell metastasistumor immune celltumor immune infiltratetumor infiltration of immune cellstumor microenvironmentαPD-L1αPD-L1 antibodiesαPD-L1 therapyαPD-L1 treatmentαPDL1
Description preview
PROJECT SUMMARY/ABSTRACT
Tumor-reactive CD8 T cells become exhausted and lose their capacity to kill cancer cells in the tumor
microenvironment. Progenitor-exhausted CD8 T cells (Tpex) found primarily in tumor-draining lymph nodes retain
their stem-like properties and respond to immune checkpoint blockade. However, our group’s recent work
suggests…
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