grant
Suppressing the Co-chaperone UNC45A reprograms the immunosuppressive tumor microenvironment to fight Cancer
NIHUS FederalResearch GrantFY2025ATR geneATR proteinATR protein kinaseATR serine/threonine kinaseAntitumor ResponseAtaxia Telangiectasia and Rad3 Related ProteinAtaxia Telangiectasia and Rad3-RelatedAtaxia-Telangiectasia and Rad3-Related GeneB blood cellsB cellB cellsB-CellsB-LymphocytesB-cellB7-H1Blood NeutrophilBlood Polymorphonuclear NeutrophilBreast CancerBreast Cancer CellBreast Cancer ModelBreast Cancer PatientBreast Tumor PatientBreast tumor modelCAGBCD274CD8 CellCD8 T cellsCD8 lymphocyteCD8+ T cellCD8+ T-LymphocyteCD8-Positive LymphocytesCD8-Positive T-LymphocytesCGCBCHEK1CHEK1 geneCHK1COX-2COX2CSF-1CSF3CSF3 geneCancer BurdenCancersCause of DeathCell BodyCell CycleCell Division CycleCell FunctionCell Growth in NumberCell MultiplicationCell PhysiologyCell ProcessCell ProliferationCell divisionCell-Cycle Checkpoint KinaseCell-Mediated Lympholytic CellsCellsCellular FunctionCellular PhysiologyCellular ProcessCellular ProliferationChIP SequencingChIP-seqChIPseqChaperoneCheckpoint kinase 1ClinicalColony-Stimulating Factor 1Cytolytic T-CellCytotoxic T CellCytotoxic T-LymphocytesDNADNA DamageDNA Damage RepairDNA InjuryDNA RepairDataDeoxyribonucleic AcidDiseaseDisorderDysfunctionFRAP-Related Protein-1FRP1FosteringFunctional disorderG-CSFGCSFGene TranscriptionGenesGenetic TranscriptionGenomicsGenotoxic StressImmuneImmune ToleranceImmune mediated therapyImmune systemImmunesImmunologic ToleranceImmunologically Directed TherapyImmunosuppressionImmunosuppression EffectImmunosuppressive EffectImmunotherapeutic agentImmunotherapyIn VitroInfiltrationIonizing Electromagnetic RadiationIonizing radiationKinasesLIAGLeftM PhaseM-CSFMAC387MEC1MGC45931MRP14Macrophage Colony-Stimulating FactorMalignant Breast NeoplasmMalignant CellMalignant NeoplasmsMalignant TumorMarrow NeutrophilMetastasisMetastasizeMetastatic LesionMetastatic MassMetastatic NeoplasmMetastatic TumorMiceMice MammalsMitosisMitosis StageMolecularMolecular ChaperonesMurineMusMyelogenousMyeloidMyeloid-derived suppressor cellsNational Cancer BurdenNeoplasm MetastasisNeutrophilic GranulocyteNeutrophilic LeukocyteNormal CellNuclearNuclear ReceptorsOutcomePD-L1PD-L1 antibodyPDL-1PGHS-2PHS-2PTGS2PTGS2 genePathway interactionsPatientsPhosphorylationPhosphotransferase GenePhosphotransferasesPhysiopathologyPlayPolymorphonuclear CellPolymorphonuclear LeukocytesPolymorphonuclear NeutrophilsPopulationProgrammed Cell Death 1 Ligand 1Programmed Death Ligand 1Protein PhosphorylationProteinsProteomicsProtocolProtocols documentationRNA ExpressionRad3 Related ProteinRadiation Induced DNA DamageRadiation Induced GenotoxicityRadiation therapyRadiation-Ionizing TotalRadiotherapeuticsRadiotherapyRefractoryRelapseS100A9S100A9 geneSCKLSCKL1Secondary NeoplasmSecondary TumorShort interfering RNASmall Interfering RNASubcellular ProcessSuspension substanceSuspensionsSystemT-CellsT-LymphocyteT8 CellsT8 LymphocytesTNBCTestingTherapeuticTranscriptionTransphosphorylasesTransplantationTumor CellTumor EscapeTumor Immune EscapeTumor ImmunityTumor-Infiltrating LymphocytesUnscheduled DNA SynthesisWomen's mortalityaPD-L1aPD-L1 antibodiesaggressive breast canceranti programmed cell death ligand 1anti programmed cell death protein ligand 1anti-PD-(L)1anti-PD-L1anti-PD-L1 antibodiesanti-PD-L1 monoclonal antibodiesanti-PDL-1anti-PDL1anti-PDL1 antibodiesanti-tumor immunityanti-tumor responseantiPD-L1antitumor immunityataxia telangiectasia and Rad3 relatedbreast tumor cellbreast tumorigenesiscancer cellcancer evasioncancer immune escapecancer immune evasioncancer immunitycancer metastasiscancer microenvironmentcell killingcell-cycle check point kinasecheck point blockadecheck point kinase 1checkpoint blockadechk1 kinasechk1 protein kinasechromatin immunoprecipitation coupled with sequencingchromatin immunoprecipitation followed by sequencingchromatin immunoprecipitation with sequencingchromatin immunoprecipitation-seqchromatin immunoprecipitation-sequencingcytokinedeath among femalesdeath among womendeath in femalesdeath in womendeath rate among womendeath rate in womenfemale deathfemale mortalityfightinghCOX-2immune check pointimmune check point blockadeimmune checkpointimmune checkpoint blockadeimmune drugsimmune microenvironmentimmune suppressionimmune suppressive activityimmune suppressive functionimmune system toleranceimmune therapeutic approachimmune therapeutic interventionsimmune therapeutic regimensimmune therapeutic strategyimmune therapyimmune unresponsivenessimmune-based therapeuticsimmune-based therapiesimmune-based treatmentsimmunecheckpointimmuno therapyimmunologic therapeuticsimmunological paralysisimmunosuppressive activityimmunosuppressive functionimmunosuppressive microenvironmentimmunosuppressive myeloid cellsimmunosuppressive responseimmunosuppressive tumor microenvironmentimmunotherapeuticsimmunotherapy agentimprovedimproved outcomein vivoindividuals with breast cancerinnovateinnovationinnovativeionizing outputkiller T cellmalignancymalignant breast tumormammary cancer modelmammary tumor modelmortality among femalesmortality among womenmortality in femalesmortality in womenmyeloid suppressor cellsmyeloid-derived suppressive cellsneoplasm/cancerneoplastic cellneutrophilnovelnucleic acid deliverypathophysiologypathwaypatient subclasspatient subclusterpatient subgroupspatient subpopulationspatient subsetspatient subtypespatients with breast cancerperson with breast cancerprogrammed cell death ligand 1programmed cell death protein ligand 1programspromoterpromotorprotein death-ligand 1radiation damage to DNAradiation treatmentradiation-induced DNA breaksrepairrepairedresistance to therapyresistant to therapyscRNA sequencingscRNA-seqsiRNAsingle cell RNA-seqsingle cell RNAseqsingle cell expression profilingsingle cell transcriptomic profilingsingle-cell RNA sequencingsuppressive myeloid cellstargeted agenttargeted drug therapytargeted drug treatmentstargeted therapeutictargeted therapeutic agentstargeted therapytargeted treatmenttherapeutic evaluationtherapeutic resistancetherapeutic testingtherapy resistantthymus derived lymphocytetranslational opportunitiestranslational potentialtransplanttreatment resistancetreatment with radiationtriple-negative breast cancertriple-negative invasive breast carcinomatumortumor cell metastasistumor eradicationtumor evasiontumor growthtumor immune evasiontumor immune microenvironmenttumor microenvironmenttumor-immune system interactionswomen's deathwomen's death rateαPD-L1αPD-L1 antibodiesαPDL1
Description preview
Abstract
Breast cancer remains one of the leading causes of death among women in the US. When available, targeted
therapies have significantly improved the outcomes for breast cancer patients. Unfortunately, resistance to
therapies and relapses are common, especially among patients with triple-negative breast cancer (TNBC), a
particularly…
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