grant
Understanding the cellular and functional changes in the immune tumor microenvironment of glioblastoma during progression and treatments.
Organization BETH ISRAEL DEACONESS MEDICAL CENTERLocation BOSTON, UNITED STATESPosted 17 Apr 2023Deadline 31 Mar 2028
NIHUS FederalResearch GrantFY2026AddressAfter CareAfter-TreatmentAftercareAnimalsAnti-OncogenesAntioncogenesAreaBone MarrowBone Marrow Reticuloendothelial SystemBrain CancerCDK4ICDKN2CDKN2 GenesCDKN2ACDKN2A geneCMM2Cancer Suppressor GenesCancersCell BodyCell CommunicationCell Communication and SignalingCell InteractionCell IsolationCell SegregationCell SeparationCell Separation TechnologyCell SignalingCell-to-Cell InteractionCellsChemotherapy and RadiationChemotherapy and/or radiationClinicalCyclin-Dependent Kinase Inhibitor 2A GeneDNA mutationData SetDevelopmentDexamethasoneEGF ReceptorEGFREGFRvIIIERBB ProteinEmerogenesEpidermal Growth Factor ReceptorEpidermal Growth Factor Receptor KinaseEpidermal Growth Factor Receptor Protein-Tyrosine KinaseEpidermal Growth Factor-Urogastrone ReceptorsEventEvolutionExperimental ModelsFlow CytofluorometriesFlow CytofluorometryFlow CytometryFlow MicrofluorimetryFlow MicrofluorometryGEM modelGEMM modelGenetic ChangeGenetic defectGenetic mutationGenetically Engineered MouseGenomicsGlial Cell TumorsGlial NeoplasmGlial TumorGlioblastomaGliomaGrade IV Astrocytic NeoplasmGrade IV Astrocytic TumorGrade IV AstrocytomaHER1HeterogeneityHortega cellHumanINK4INK4AImmuneImmune infiltratesImmune mediated therapyImmunesImmunologically Directed TherapyImmunologyImmunosuppressionImmunosuppression EffectImmunosuppressive EffectImmunotherapyInfiltrationInflammatoryInstitutionInternationalIntracellular Communication and SignalingIonizing Electromagnetic RadiationIonizing radiationKnowledgeLesionMMAC1MMAC1 proteinMTS1MTS1 GenesMacrophageMalignantMalignant - descriptorMalignant CellMalignant NeoplasmsMalignant TumorMalignant Tumor of the BrainMalignant neoplasm of brainMapsMediatingMiceMice MammalsMicrogliaModalityModern ManMolecularMouse StrainsMurineMusMutated in Multiple Advanced Cancers 1MutationMyelogenousMyeloidMyeloid CellsMyeloid-derived suppressor cellsMφNatureNeuroglial NeoplasmNeuroglial TumorOnco-Suppressor GenesOncogenes-Tumor SuppressorsOutputPHTS genePHTS proteinPTENPTEN genePTEN proteinPTEN1PathologyPathway interactionsPatientsPhosphatase and Tensin HomologPhosphatase and Tensin Homolog Deleted on Chromosome 10PopulationPopulation DynamicsPropertyRNA SeqRNA sequencingRNAseqRadiationRadiation-Ionizing TotalReactionRecessive OncogenesResearchResistanceSamplingSignal TransductionSignal Transduction SystemsSignalingSpatial DistributionT-CellsT-LymphocyteTCGATGF-alpha ReceptorTP16TSG9ATechnologyTemodalTemodarThe Cancer Genome AtlasTherapeuticTimeTransforming Growth Factor alpha ReceptorTumor CellTumor Suppressing GenesTumor Suppressor GenesTumor-infiltrating immune cellsUrogastrone Receptoranalyzing longitudinalbiological signal transductionc-erbB-1c-erbB-1 Proteincancer cellcancer immunologycell sortingcheck point blockadecheck point immunotherapycheck point inhibitioncheck point inhibitor therapycheck point inhibitory therapycheck point therapycheckpoint blockadecheckpoint immunotherapycheckpoint inhibitioncheckpoint inhibitor therapycheckpoint inhibitory therapycheckpoint therapychemo/radiation therapychemotherapy and radiotherapyclinical relevanceclinical significanceclinically relevantclinically significantdesigndesigningdevelopmentaleffective therapyeffective treatmentepidermal growth factor receptor VIIIerbB-1erbB-1 Proto-Oncogene ProteinerbBlflow cytophotometrygenetically engineered mouse modelgenetically engineered murine modelgenome mutationgitter cellglial-derived tumorglioblastoma multiformehuman dataimmune cell infiltrateimmune cell infiltration of tumorsimmune cells infiltrating the tumorimmune cells that infiltrate the tumorimmune check point blockadeimmune check point inhibitionimmune check point therapyimmune checkpoint blockadeimmune checkpoint inhibitionimmune checkpoint therapyimmune microenvironmentimmune resistanceimmune suppressionimmune suppressive activityimmune suppressive functionimmune therapeutic approachimmune therapeutic interventionsimmune therapeutic regimensimmune therapeutic strategyimmune therapyimmune-based therapiesimmune-based treatmentsimmune-resistantimmuno therapyimmunoresistanceimmunosuppressive activityimmunosuppressive functionimmunosuppressive microenvironmentimmunosuppressive myeloid cellsimmunosuppressive responseimmunosuppressive tumor microenvironmentinfiltration of tumors by immune cellsinsightintratumoral immune cellintratumoral immune infiltrateionizing outputlongitudinal analysismalignancymembermesogliamethazolastonemicroglial cellmicrogliocytemouse modelmultiomicsmultiple omicsmultiplexed imagingmurine modelmutantmutated in multiple advanced cancers 1 proteinmyeloid suppressor cellsmyeloid-derived suppressive cellsneoplasm immunologyneoplasm/cancerneoplasticneoplastic cellneuroglia neoplasmneuroglia tumornew drug targetnew druggable targetnew pharmacotherapy targetnew therapeutic approachnew therapeutic interventionnew therapeutic strategiesnew therapeutic targetnew therapy approachesnew therapy targetnew treatment approachnew treatment strategynovel drug targetnovel druggable targetnovel pharmacotherapy targetnovel therapeutic approachnovel therapeutic interventionnovel therapeutic strategiesnovel therapeutic targetnovel therapy approachnovel therapy targetoncosuppressor geneoverexpressoverexpressionp14ARFp16 Genesp16INK4 Genesp16INK4A Genesp16INK4apanomicspathwayperivascular glial cellphosphatase and tensin homologue on chromosome tenpost treatmentpre-clinicalpreclinicalprotein biomarkersprotein markersproto-oncogene protein c-erbB-1radiation or chemotherapyrecruitresistantscRNA sequencingscRNA-seqsingle cell RNA-seqsingle cell RNAseqsingle cell analysissingle cell expression profilingsingle cell transcriptomic profilingsingle-cell RNA sequencingspatial RNA sequencingspatial gene expression analysisspatial gene expression profilingspatial multiomicsspatial omicsspatial resolved transcriptome sequencingspatial transcriptome analysisspatial transcriptome profilingspatial transcriptome sequencingspatial transcriptomicsspatial tri-omicsspatially resolved transcriptomicsspatio transcriptomicsspongioblastoma multiformestandard of caresuccesssuppressive myeloid cellstargeted drug therapytargeted drug treatmentstargeted therapeutictargeted therapeutic agentstargeted therapytargeted treatmenttemozolomidetherapeutic agent developmenttherapeutic developmentthymus derived lymphocytetranscriptome sequencingtranscriptomic sequencingtumortumor immune celltumor immune infiltratetumor immune microenvironmenttumor immunologytumor infiltration of immune cellstumor-immune system interactionstumorigenic
Description preview
Project Summary
Glioblastoma (GBM) is an incurable primary malignant brain cancer characterized by a high degree of
interpatient and intratumoral genomic and cellular heterogeneity, a brief median survival (~15 months), and
absence of an effective treatment. Even the successes of checkpoint blockade immunotherapies observed in
many cancers have…
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