grant
Spatiotemporal molecular elucidation of radiation-induced tumor microenvironment remodeling to en-hance immunotherapy in head and neck cancer
Organization PROVIDENCE HEALTH & SERVICES - OREGONLocation RENTON, UNITED STATESPosted 1 May 2026Deadline 30 Apr 2031
NIHUS FederalResearch GrantFY2026AbscissionAdjuvantAffectAfter CareAfter-TreatmentAftercareAnimal ModelAnimal Models and Related StudiesAntigen PresentationAntigensAntitumor ResponseBiological MarkersBiopsyBody TissuesCD8 CellCD8 T cellsCD8 lymphocyteCD8+ T cellCD8+ T-LymphocyteCD8-Positive LymphocytesCD8-Positive T-LymphocytesCancersCell AdhesionCell BodyCell CommunicationCell DifferentiationCell Differentiation processCell Growth in NumberCell InteractionCell MaturationCell MultiplicationCell ProliferationCell-to-Cell InteractionCellsCellular AdhesionCellular Immune FunctionCellular ProliferationChemotactic CytokinesCirculationClass I GenesClinicalClinical TrialsClone CellsDendritic CellsDevelopmentDoseEffectivenessEffector CellExcisionExhibitsExpression SignatureExtirpationGene Expression ProfileHNC patientHNSCCHPVHPV [-]HPV associated HNSCCHPV driven HNSCCHPV driven head and neck cancerHPV negativeHPV positiveHPV(+)HPV(+) HNSCCHPV(+) head and neck squamous cell carcinomaHPV(-)HPV(-) HNSCCHPV(-) head and neck squamous cell carcinomaHPV+HPV+ HNSCCHPV+ head and neck cancersHPV- HNSCCHPV-associated head and neck cancerHPV-associated head and neck squamous cell carcinomaHPV-negative HNSCCHPV-negative head and neck cancerHPV-negative head and neck squamous cell carcinomaHPV-positive HNSCCHPV-positive head and neck cancersHPV-related HNSCCHPV-related head and neck squamous cell carcinomaHead and Neck CancerHead and Neck CarcinomaHead and Neck Squamous Cell CarcinomaHomologous Chemotactic CytokinesHuman Papilloma VirusHuman PapillomavirusHuman papillomavirus driven HNSCCHuman papillomavirus driven head and neck cancerImmuneImmune Cell ActivationImmune TargetingImmune mediated therapyImmunesImmunohistochemistryImmunohistochemistry Cell/TissueImmunohistochemistry Staining MethodImmunologically Directed TherapyImmunomodulationImmunoradiotherapyImmunotherapyIn complete remissionInduction TherapyInfectious Human Wart VirusIntercrinesKeytrudaLymph Node Reticuloendothelial SystemLymph node properLymphaticLymphatic nodesMHC Class IMHC Class I GenesMHC ReceptorMacrophage ActivationMajor Histocompatibility Complex ReceptorMalignant Head and Neck NeoplasmMalignant NeoplasmsMalignant TumorMediatingMetastatic/RecurrentModelingMolecularMonitorNEOADJNeoadjuvantNeoadjuvant TherapyNeoadjuvant TreatmentNivolumabNodalOpdivoOperative ProceduresOperative Surgical ProceduresOutcomePD 1PD-1PD1PathologicPathway interactionsPatient outcomePatient-Centered OutcomesPatient-Focused OutcomesPatientsPeptidesPerformancePhagocytesPhagocytic CellPhasePhase 3 Clinical TrialsPhase III Clinical TrialsPrimary NeoplasmPrimary TumorProteomicsRadiationRadiation therapyRadioimmunotherapyRadiotherapeuticsRadiotherapyRemovalResearchResearch SpecimenRoleSCCHNSIS cytokinesSamplingSentinelSentinel Lymph NodeSentinel Lymph Node BiopsySentinel NodeSentinel Node BiopsySpecimenSuppressor CellsSuppressor-Effector T-CellsSuppressor-Effector T-LymphocytesSurgicalSurgical InterventionsSurgical ProcedureSurgical RemovalT Suppressor CellT cell infiltrationT-Cell Antigen ReceptorsT-Cell ReceptorT-CellsT-LymphocyteT-cell receptor repertoireT8 CellsT8 LymphocytesTCR repertoireTestingTh-1 CellTh-2 CellTh1 CellsTh2 CellsTimeTissuesTumor CellTumor ImmunityTumor VolumeTumor-infiltrating immune cellsType 1 Helper CellType 2 Helper CellUpregulationVeiled CellsWorkabsence of HPVabsence of human papillomavirusamebocyteanti-canceranti-cancer immunotherapyanti-tumor immunityanti-tumor responseanticancer immunotherapyantitumor immunitybio-markersbiologic markerbiomarkercancer immunitycancer immunotherapycancer microenvironmentcell typecellular differentiationcheck point blockadecheck point immunotherapycheck point inhibitor therapycheck point inhibitory therapycheck point therapycheckpoint blockadecheckpoint immunotherapycheckpoint inhibitor therapycheckpoint inhibitory therapycheckpoint therapychemo-/radio-therapychemo-radiotherapychemoattractant cytokinechemokinechemoradiationchemoradiation therapychemoradiation treatmentchemoradiotherapycohortcomplete responsedeep learning based modeldeep learning modeldevelopmentaldraining lymph nodefirst in manfirst-in-humangene expression patterngene expression signaturegene panelglobal gene expressionglobal transcription profilehead and neck cancer patienthead and neck squamous carcinomahead and neck squamous cell cancerhead/neck cancerhuman papilloma virus+ head and neck squamous cell carcinomahuman papillomavirus (-) head and neck squamous cell carcinomahuman papillomavirus +human papillomavirus - head and neck squamous cell carcinomahuman papillomavirus associated head and neck cancerhuman papillomavirus associated head and neck squamous cell carcinomahuman papillomavirus driven head and neck squamous cell carcinomahuman papillomavirus induced head and neck squamous cell carcinomahuman papillomavirus negativehuman papillomavirus negative head and neck cancerhuman papillomavirus negative head and neck squamous cell carcinomahuman papillomavirus positivehuman papillomavirus positive HNSCChuman papillomavirus positive head and neck cancershuman papillomavirus positive head and neck squamous cell carcinomahuman papillomavirus related head and neck squamous cell carcinomahuman papillomavirus- head and neck squamous cell carcinomaimmune activationimmune cell infiltration of tumorsimmune cells infiltrating the tumorimmune cells that infiltrate the tumorimmune check point blockadeimmune check point therapyimmune checkpoint blockadeimmune checkpoint therapyimmune functionimmune modulationimmune regulationimmune therapeutic approachimmune therapeutic interventionsimmune therapeutic regimensimmune therapeutic strategyimmune therapyimmune-based cancer therapiesimmune-based therapiesimmune-based treatmentsimmuno therapyimmunogenimmunologic reactivity controlimmunomodulatoryimmunoregulationimmunoregulatoryimmunotherapy for cancerimmunotherapy of cancerimprovedimproved outcomeinduction therapiesinfiltration of tumors by immune cellsintratumoral immune cellintratumoral immune infiltratelymph glandlymph nodeslymphatic drainagelymphnodesmalignancymalignant head and neck tumormodel of animalmultigene panelmultiomicsmultiple omicsneoplasm/cancerneoplastic cellnew therapeutic approachnew therapeutic interventionnew therapeutic strategiesnew therapy approachesnew treatment approachnew treatment strategynext generationnon-HPV HNSCCnon-human papillomavirus head and neck squamous cell carcinomanovelnovel therapeutic approachnovel therapeutic interventionnovel therapeutic strategiesnovel therapy approachoral HPV-positive HNSCCoral HPV-positive head and neck cancersoral human papillomavirus positive head and neck cancersoral human papillomavirus positive head and neck squamous cell carcinomapanomicspathwaypatient oriented outcomespatient prognosispembrolizumabperipheral bloodphase 1 trialphase I trialphase III protocolpost treatmentpredictive biological markerpredictive biomarkerspredictive markerpredictive molecular biomarkerpresence of HPVpresence of human papillomaviruspreservationprogrammed cell death 1programmed cell death protein 1programmed death 1radiation effectradiation treatmentradio-chemo-therapyradio-chemotherapyradiochemotherapyrecruitregional lymph noderesectionresponders and non-respondersresponders from non-respondersresponders or non-respondersresponders versus non-respondersresponders vs non-respondersresponders/nonrespondersresponsesle2social rolespatial RNA sequencingspatial and temporalspatial gene expression analysisspatial gene expression profilingspatial resolved transcriptome sequencingspatial temporalspatial transcriptome analysisspatial transcriptome profilingspatial transcriptome sequencingspatial transcriptomicsspatially resolved transcriptomicsspatio transcriptomicsspatiotemporalstandard of caresuppressor T lymphocytesurgerysystemic lupus erythematosus susceptibility 2thymus derived lymphocytetraffickingtranscriptional profiletranscriptional signaturetranscriptometreatment with radiationtumortumor immune celltumor immune infiltratetumor infiltration of immune cellstumor microenvironmentwart virus
Description preview
Project Summary
Recently we showed in HNSCC models that effective checkpoint blockade is dependent upon intact lymphatic
drainage for dendritic cell trafficking and that elective nodal radiation abrogated the effectiveness of
immunotherapy, possibly explaining the lack of efficacy seen in prior studies. Neoadjuvant immunotherapy
preserves draining…
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