grant
Adverse gut microbiome promotes resistance immune checkpoint inhibitors via chronic inflammation
Organization UNIVERSITY OF TX MD ANDERSON CAN CTRLocation HOUSTON, UNITED STATESPosted 1 Jan 2025Deadline 31 Dec 2028
NIHUS FederalResearch GrantFY2026Antibiotic AgentsAntibiotic DrugsAntibioticsAntigen-Presenting CellsAntigensAutomobile DrivingB cell differentiation factorB cell stimulating factor 2B-Cell Differentiation FactorB-Cell Differentiation Factor-2B-Cell Stimulatory Factor-2BCDFBSF-2BSF2BacteriaBlood SerumCD11cCD8 CellCD8 T cellsCD8 lymphocyteCD8+ T cellCD8+ T-LymphocyteCD8-Positive LymphocytesCD8-Positive T-LymphocytesCancer PatientCancersCaringCell BodyCell Communication and SignalingCell LineCell SignalingCell WallCellLineCellsCheckpoint inhibitorChronicClinicalClinical TrialsDataDendritic CellsDevelopmentDonor personFecesGI microbiomeGenesGrawitz TumorHPGFHepatocyte-Stimulating FactorHigh-Frequency Microsatellite InstabilityHybridoma Growth FactorHypernephroid CarcinomaHypernephromaIFN-beta 2IFNB2IL-1IL-1 ReceptorsIL-6IL1IL1 ReceptorsIL6 ProteinITGAXITGAX geneImmuneImmune checkpoint inhibitorImmune systemImmunesImmunityImpairmentInfiltrationInflammationInflammation MediatorsInflammatoryInflammatory ResponseInterleukin IInterleukin-1Interleukin-1 ReceptorsInterleukin-6InterleukinsIntracellular Communication and SignalingInvestmentsLipopolysaccharidesLymphocyte-Stimulating HormoneMGI-2MSI-HMacrophage Cell FactorMalignant MelanomaMalignant NeoplasmsMalignant TumorMeasuresMediatingMelanomaMelanoma MetastasisMelanoma patientMentorsMentorshipMeta-AnalysisMetastasisMetastasizeMetastatic LesionMetastatic MassMetastatic MelanomaMetastatic NeoplasmMetastatic TumorMiceMice MammalsMicrosatellite InstabilityMiscellaneous AntibioticModelingMolecular MimicryMurineMusMyelogenousMyeloidMyeloid CellsMyeloid Differentiation-Inducing ProteinNSCLCNSCLC - Non-Small Cell Lung CancerNeoplasm MetastasisNephroid CarcinomaNon-Small Cell Lung CancerNon-Small-Cell Lung CarcinomaOncologyOncology CancerOutcomePD-1 antibody therapyPD-1 therapyPD1 antibody therapyPD1 based treatmentPatientsPhasePhysiciansPlasmacytoma Growth FactorPositionPositioning AttributeProbioticsReceptor ActivationReceptor SignalingRefractoryRenal AdenocarcinomaRenal Cell AdenocarcinomaRenal Cell CancerRenal Cell CarcinomaResearchResistanceRoleSamplingScientistSecondary NeoplasmSecondary TumorSeminalSerumSignal TransductionSignal Transduction SystemsSignalingStrains Cell LinesT Helper FactorT cell receptor repertoire sequencingT cell receptor sequencingT-CellsT-LymphocyteT8 CellsT8 LymphocytesTCR repertoire sequencingTCR sequencingTCR-seqTCRseqTLR proteinTestingTissue SampleToll-Like Receptor Family GeneToll-like receptorsTumor ImmunityVeiled CellsWild Type MouseWorkaCTLA-4aCTLA-4 antibodiesaCTLA4aPD-1 therapyaPD-1 treatmentaPD1 therapyaPD1 treatmentaccessory cellanalyzing longitudinalanti-CTLA-4anti-CTLA-4 antibodiesanti-CTLA4anti-CTLA4 antibodiesanti-PD-1 therapyanti-PD-1 treatmentanti-PD1 therapyanti-PD1 treatmentanti-cancer immunotherapyanti-programmed cell death 1 therapyanti-programmed cell death protein 1 therapyanti-tumor immunityanticancer immunotherapyantitumor immunitybiological signal transductionbowel inflammationcancer immunitycancer immunotherapycancer metastasiscancer typecareer developmentcheck point immunotherapycheck point inhibitor therapycheck point inhibitory therapycheck point therapycheckpoint immunotherapycheckpoint inhibitor therapycheckpoint inhibitory therapycheckpoint therapyclinical efficacycohortcultured cell linecytokinedevelopmentaldigestive tract microbiomedrivingearly clinical trialearly phase clinical trialenteric microbiomeexperimentexperimental researchexperimental studyexperimentsfecal microbial transplantationfecal microbiome transplantationfecal microbiota transplantfecal microbiota transplantationfecal transplantfecal transplantationgastrointestinal microbiomegut inflammationgut microbiomegut-associated microbiomeimmune check point inhibitorimmune check point therapyimmune checkpoint therapyimmune resistanceimmune-based cancer therapiesimmune-resistantimmunogenimmunogenicimmunoresistanceimmunotherapy for cancerimmunotherapy of cancerimproved outcomeinflamed bowelinflamed gutinflamed intestineinflammatory mediatorinterferon beta 2intestinal biomeintestinal inflammationintestinal microbiomekidney adenocarcinomalongitudinal analysislymphocyte activating factormalignancymicrobialmicrobiomemicrobiome interventionmicrobiome therapeuticsmicrobiome therapymicrobiome treatmentmicrobiome-based interventionmicrobiome-based therapeuticmicrobiome-based therapymicrobiome-based treatmentmouse modelmultidisciplinarymurine modelneoplasm/cancernext generationpatients suffering from melanomapatients with melanomaprogrammed cell death protein 1 therapyprogramsresistance mechanismresistantresistant mechanismresponsescRNA sequencingscRNA-seqsingle cell RNA-seqsingle cell RNAseqsingle cell expression profilingsingle cell transcriptomic profilingsingle-cell RNA sequencingsocial rolespatial RNA sequencingspatial gene expression analysisspatial gene expression profilingspatial resolved transcriptome sequencingspatial transcriptome analysisspatial transcriptome profilingspatial transcriptome sequencingspatial transcriptomicsspatially resolved transcriptomicsspatio transcriptomicsstoolsystemic inflammationsystemic inflammatory responsethymus derived lymphocytetransplant donortumortumor cell metastasistumor growthwildtype mouseα-CTLA-4α-CTLA4αCTLA-4αCTLA4
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Project summary/abstract
Immune checkpoint inhibitors (ICI) transformed oncological care for multiple cancers. Yet, 80% of ICI patients
will eventually fail therapy. Colossal efforts are invested in overcoming ICI resistance. A promising candidate
is the gut microbiome which was associated with ICI clinical outcomes. I led a seminal clinical trial…
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