grant
Re-engineering differential regulation of ferroptosis in melanoma microenvironment
Organization UNIVERSITY OF PITTSBURGH AT PITTSBURGHLocation PITTSBURGH, UNITED STATESPosted 12 Jul 2023Deadline 30 Jun 2028
NIHUS FederalResearch GrantFY2025AccelerationAffectAlcohol Chemical ClassAlcoholsApoptosisApoptosis PathwayBlood NeutrophilBlood Polymorphonuclear NeutrophilBlood SampleBlood monocyteBlood specimenBuckytubesCancer TreatmentCancersCarbon NanotubesCarbon nano tubesCell BodyCell Communication and SignalingCell DeathCell DifferentiationCell Differentiation processCell SignalingCellsCessation of lifeCheckpoint inhibitorClinicalComplementary interventionComplementary therapiesComplementary treatmentComplexDataDeathDeath RateDevelopmentEngineeringFatty Acid HydroperoxidesFe elementGeneticGenetic ModelsGlutathioneGoalsHumanImmuneImmune ToleranceImmune checkpoint inhibitorImmune mediated therapyImmunesImmunologic ToleranceImmunologically Directed TherapyImmunomodulationImmunosuppressionImmunosuppression EffectImmunosuppressive EffectImmunotherapyIn VitroInfiltrationIntracellular Communication and SignalingIonsIronLipid HydroperoxideLipid PeroxidationLipid PeroxidesLipidsLipoperoxidesLytotoxicityMEKsMacrophageMalignantMalignant - descriptorMalignant CellMalignant MelanomaMalignant Neoplasm TherapyMalignant Neoplasm TreatmentMalignant NeoplasmsMalignant TumorMarrow NeutrophilMarrow monocyteMass Photometry/Spectrum AnalysisMass SpectrometryMass SpectroscopyMass SpectrumMass Spectrum AnalysesMass Spectrum AnalysisMeasuresMediatingMelaninsMelanogenesisMelanomaMelanoma CellMelanoma TumorMelanoma patientMetastatic Skin CancerMetastatic Skin CarcinomaMethodsMiceMice MammalsModelingModern ManModernizationMurineMusMyelogenousMyeloidMyeloid CellsMyeloid-derived suppressor cellsMφNanodeliveryNeoplasm TransplantationNeutrophilic GranulocyteNeutrophilic LeukocyteOutcomeOxidation-ReductionPH-GPeroxidasePHGPx enzymePathway interactionsPatientsPolymorphonuclear CellPolymorphonuclear LeukocytesPolymorphonuclear NeutrophilsPopulationPredispositionProcessProgrammed Cell DeathPublishingRedoxRefractoryRegulationResistanceSamplingSignal TransductionSignal Transduction SystemsSignalingSusceptibilitySystemT-CellsT-LymphocyteTestingTherapeuticTissue SampleTumor CellTumor ImmunityTumor TissueTumor growth in melanomaTumor-infiltrating immune cellsalternative treatmentanalytical toolanti-cancer therapyanti-tumor immune responseanti-tumor immunityantitumor immunitybiological signal transductioncancer cellcancer immunitycancer microenvironmentcancer progressioncancer therapycancer-directed therapycell typecellular differentiationcheck point immunotherapycheck point inhibitor therapycheck point inhibitory therapycheck point therapycheckpoint immunotherapycheckpoint inhibitor therapycheckpoint inhibitory therapycheckpoint therapyclinical relevanceclinically relevantcytotoxiccytotoxicitydevelopmentaldisabledgamma-L-Glu-L-Cys-Glygamma-L-Glutamyl-L-Cysteinylglycineglutathione peroxidase GPX4grapheneimage-based methodimaging methodimaging modalityimmune cell infiltration of tumorsimmune cells infiltrating the tumorimmune cells that infiltrate the tumorimmune check pointimmune check point inhibitorimmune check point therapyimmune checkpointimmune checkpoint therapyimmune modulating strategyimmune modulationimmune modulatory strategyimmune regulationimmune suppressionimmune suppressive activityimmune suppressive functionimmune system toleranceimmune therapeutic approachimmune therapeutic interventionsimmune therapeutic regimensimmune therapeutic strategyimmune therapyimmune unresponsivenessimmune-based therapiesimmune-based treatmentsimmunecheckpointimmuno therapyimmunogenicimmunologic reactivity controlimmunological paralysisimmunomodulatoryimmunomodulatory strategyimmunoregulationimmunoregulatoryimmunosuppressive activityimmunosuppressive functionimmunosuppressive myeloid cellsimmunosuppressive responseimprovedin vivoinfiltration of tumors by immune cellsinhibitorintratumoral immune cellintratumoral immune infiltratelipid peroxidelipidomicsmalignancymonocytemortality ratemortality ratiomyeloid suppressor cellsmyeloid-derived suppressive cellsnanodotnanomaterialsnecrocytosisneoplasm progressionneoplasm/cancerneoplastic cellneoplastic progressionneutrophilnew approachesnew drug treatmentsnew drugsnew pharmacological therapeuticnew therapeuticsnew therapynext generation therapeuticsnovelnovel approachesnovel drug treatmentsnovel drugsnovel pharmaco-therapeuticnovel pharmacological therapeuticnovel strategiesnovel strategynovel therapeuticsnovel therapyoxidationoxidation reduction reactionpathwaypatients suffering from melanomapatients with melanomapharmacologicphospholipid-hydroperoxide glutathione peroxidasepreventpreventingquantumrepairrepairedresistantspatial and temporalspatial temporalspatiotemporalstandard of caresuppressive myeloid cellsthymus derived lymphocytetumortumor growthtumor immune celltumor immune infiltratetumor infiltration of immune cellstumor microenvironmenttumor progressiontumor transplanttumor transplantation
Description preview
Project Summary
Melanoma is an aggressive and highly metastatic skin cancer. Although modern combination checkpoint
inhibitors revolutionized clinical outcomes in advanced cases, over half of all patients are refractory to
immunotherapy and require alternative or complementary treatment options. The discovery of ferroptosis
provided a novel way to…
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