grant
Metabolic reprogramming to boost the fitness of anti-tumor immunity against metastatic colon cancer
Organization COLD SPRING HARBOR LABORATORYLocation COLD SPRING HARBOR, UNITED STATESPosted 1 Apr 2025Deadline 31 Mar 2030
NIHUS FederalResearch GrantFY2026ATAC sequencingATAC-seqATACseqAffectAnti-InflammatoriesAnti-Inflammatory AgentsAnti-inflammatoryAntitumor ResponseAssay for Transposase-Accessible Chromatin using sequencingAutologousBasal Transcription FactorBasal transcription factor genesCAR T cellsCAR modified T cellsCAR-TCAR-TsCD8 CellCD8 T cellsCD8 lymphocyteCD8+ T cellCD8+ T-LymphocyteCD8-Positive LymphocytesCD8-Positive T-LymphocytesCPT 1CUT&RUNCancer CauseCancer EtiologyCancer TreatmentCancersCarnitine Acyltransferase ICarnitine O-PalmitoyltransferaseCarnitine PalmitoyltransferaseCarnitine Palmitoyltransferase ICatabolismCell BodyCell Communication and SignalingCell FunctionCell PhysiologyCell ProcessCell SignalingCellsCellular FunctionCellular Metabolic ProcessCellular PhysiologyCellular ProcessCessation of lifeChimera ProteinChimeric ProteinsCleavage Targets and Release Using NucleaseCleavage Under Targets and Release Using NucleaseClonal ExpansionColorectal CancerDNA mutationDataDeathDiseaseDisorderEGF ReceptorEGFRERBB ProteinERBB2ERBB2 geneEffectivenessElementsEnsureEnzyme GeneEnzymesEpidermal Growth Factor ReceptorEpidermal Growth Factor Receptor KinaseEpidermal Growth Factor Receptor Protein-Tyrosine KinaseEpidermal Growth Factor-Urogastrone ReceptorsEpigeneticEpigenetic ChangeEpigenetic MechanismEpigenetic ProcessEquilibriumFaceFatty AcidsFusion ProteinGeneral Transcription Factor GeneGeneral Transcription FactorsGeneticGenetic ChangeGenetic defectGenetic mutationGoalsHER -2HER-2HER1HER2HER2 GenesHER2/neuHumanImmuneImmune EvasionImmune TargetingImmune mediated therapyImmune responseImmune systemImmunesImmunityImmunologically Directed TherapyImmunotherapeutic agentImmunotherapyIn VitroIncidenceIndividualInflammatoryIntestinalIntestinesIntracellular Communication and SignalingKO miceKnock-out MiceKnockout MiceLaboratoriesLipidsLiteratureLytotoxicityMalignant CellMalignant Neoplasm TherapyMalignant Neoplasm TreatmentMalignant NeoplasmsMalignant TumorMeasuresMediatingMetabolicMetastasisMetastasizeMetastatic LesionMetastatic MassMetastatic NeoplasmMetastatic TumorMethodsMiceMice MammalsMicrosatellite MarkersMicrosatellite RepeatsMicrosatellitesMitochondriaModalityModelingModern ManModificationMurineMusMutationNEU OncogeneNEU proteinNeoplasm MetastasisNull MouseOncogene ErbB2OncogenesisOrganoidsOutcomePD-1 antibodyPD-1 blockadePD1 antibodyPD1 blockadePPAR deltaPPAR-δPPARD proteinPPARdeltaPPARδPalmitoylcarnitine TransferasePalmitylcarnitine AcyltransferasePatientsPeroxisome Proliferator-Activated Receptor deltaPeroxisome Proliferator-Activated Receptor δPopulationProgenitor CellsPrognosisQOLQOL improvementQuality of lifeRNA SeqRNA sequencingRNAseqReportingResearchRoleSecondary NeoplasmSecondary TumorSignal TransductionSignal Transduction SystemsSignalingSubcellular ProcessSurvival RateT cells for CART-CellsT-LymphocyteT8 CellsT8 LymphocytesTGF-alpha ReceptorTKR1TamoxifenTestingTherapeuticTranscription Factor Proto-OncogeneTranscription factor genesTransforming Growth Factor alpha ReceptorTreatment EfficacyTreatment outcomeTumor ImmunityUrogastrone ReceptorVP 16VP16WomanaPD-1aPD1anti programmed cell death 1anti-PD-1anti-PD-1 Abanti-PD-1 antibodiesanti-PD-1 blockadeanti-PD-1 monoclonal antibodiesanti-PD1anti-PD1 Abanti-PD1 antibodiesanti-PD1 blockadeanti-PD1 monoclonal antibodiesanti-cancer therapyanti-programmed cell death protein 1anti-programmed cell death protein 1 antibodiesanti-programmed death-1 antibodyanti-tumor effectanti-tumor immunityanti-tumor responseantiPD-1antitumor effectantitumor immunityassay for transposase accessible chromatin followed by sequencingassay for transposase accessible chromatin seqassay for transposase accessible chromatin sequencingassay for transposase-accessible chromatin with sequencingbalancebalance functionbiological signal transductionbowelc-erbB-1c-erbB-1 Proteinc-erbB-2c-erbB-2 Genesc-erbB-2 Proto-Oncogenescancer cellcancer immunitycancer metastasiscancer microenvironmentcancer progressioncancer therapycancer-directed therapycarnitine palmitoyltransferase 1cell metabolismcell typecellular metabaolismcheck point blockadecheckpoint blockadechimeric antigen T cell receptorchimeric antigen receptor (CAR) T cellschimeric antigen receptor Tchimeric antigen receptor T cellschimeric antigen receptor fusion protein T-cellschimeric antigen receptor modified T cellsclinical relevanceclinically relevantcolon cancer patientscolorectal cancer patientscolorectal cancer progressioncolorectal cancer therapycolorectal cancer treatmentcytotoxicityeffective therapyeffective treatmentepigeneticallyerbB-1erbB-1 Proto-Oncogene ProteinerbB-2 GeneserbBlfacesfacialfatty acid oxidationfightingfitnessgain of functiongenome mutationherstatinhost responseimmune check point blockadeimmune checkpoint blockadeimmune drugsimmune evasiveimmune microenvironmentimmune system responseimmune therapeutic approachimmune therapeutic interventionsimmune therapeutic regimensimmune therapeutic strategyimmune therapyimmune-based therapeuticsimmune-based therapiesimmune-based treatmentsimmuno therapyimmunogenicimmunogenicityimmunologic therapeuticsimmunoresponseimmunosuppressive microenvironmentimmunosuppressive tumor microenvironmentimmunotherapeuticsimmunotherapy agentimprovedimprovements in QOLimprovements in quality of lifein vivoinnovateinnovationinnovativeinsightintervention efficacyloss of functionmalignancymenmetabolic fitnessmetastatic colo-rectalmetastatic colo-rectal cancermetastatic colo-rectal carcinomametastatic colon cancermetastatic colorectalmetastatic colorectal cancermetastatic colorectal carcinomamitochondrialmortalitymouse modelmurine modelneoplasm progressionneoplasm/cancerneoplastic progressionneu Genesnew drug treatmentsnew drugsnew pharmacological therapeuticnew therapeuticsnew therapynext generation therapeuticsnovel drug treatmentsnovel drugsnovel pharmaco-therapeuticnovel pharmacological therapeuticnovel therapeuticsnovel therapyoxidationpharmacologicproto-oncogene protein c-erbB-1quality of life improvementsocial rolestem cellssynergismtherapeutic efficacytherapy efficacythymus derived lymphocytetranscription factortranscriptome sequencingtranscriptomic sequencingtumortumor cell metastasistumor growthtumor immune microenvironmenttumor initiationtumor microenvironmenttumor progressiontumor-immune system interactionstumorigenesisαPD-1αPD1
Description preview
Abstract
The primary goal of this project is to enhance the efficacy of immunotherapy against metastatic colorectal cancer
(mCRC) by activating the peroxisome proliferator-activated receptor delta (PPARδ)-Carnitine
palmitoyltransferase 1a (Cpt1a) axis in CD8+ T cells. Colorectal cancer (CRC) is among the deadliest cancers
worldwide, with rising…
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