Transcriptional repression by HDAC3 mediates T cell exclusion from Kras mutant lung tumors
McGuire C, Meehan A, Couser E, Bull L, Minor A, Kuhlmann-Hogan A, Kaech S, Shaw R, Eichner L. Transcriptional repression by HDAC3 mediates T cell exclusion from Kras mutant lung tumors. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2317694121. PMID: 39388266, PMCID: PMC11494357, DOI: 10.1073/pnas.2317694121.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBenzamidesCell Line, TumorChemokine CXCL10Gene Expression Regulation, NeoplasticHistone Deacetylase InhibitorsHistone DeacetylasesHumansLung NeoplasmsMiceMutationProto-Oncogene Proteins p21(ras)PyridinesPyridonesPyrimidinonesT-LymphocytesTranscription, GeneticTumor MicroenvironmentConceptsT cell recruitmentLung tumorsHistone deacetylase 3Enhanced T cell recruitmentCombined treatmentLung tumors in vivoGenetically engineered mouse modelsT cell exclusionInhibition of histone deacetylase 3Tumor immune microenvironmentTumor growth controlKRAS mutant lung tumorsTumors in vivoLung cancer cellsImmune microenvironmentT cellsTissue-specific fashionMouse modelPathway inhibitorTumorPharmacological inhibitionCancer cellsFunction in vivoTranscriptional regulationTranscriptional repressionACLY and ACSS2 link nutrient-dependent chromatin accessibility to CD8 T cell effector responses
Kaymak I, Watson M, Oswald B, Ma S, Johnson B, DeCamp L, Mabvakure B, Luda K, H. E, Lau K, Fu Z, Muhire B, Kitchen-Goosen S, Vander Ark A, Dahabieh M, Samborska B, Vos M, Shen H, Fan Z, Roddy T, Kingsbury G, Sousa C, Krawczyk C, Williams K, Sheldon R, Kaech S, Roy D, Jones R. ACLY and ACSS2 link nutrient-dependent chromatin accessibility to CD8 T cell effector responses. Journal Of Experimental Medicine 2024, 221: e20231820. PMID: 39150482, PMCID: PMC11329787, DOI: 10.1084/jem.20231820.Peer-Reviewed Original ResearchConceptsAcyl-CoA synthetase short-chain family member 2Acetyl-CoA productionATP citrate lyaseChromatin accessibilityAcetyl-CoAEnzyme ATP citrate lyaseFamily member 2Function in vivoCoordination of cellular metabolismTCA cycleMetabolic nodesGene locusCitrate lyaseT cell effector responsesHistone acetylationCellular metabolismEffector functionsCD8 T cellsResponse to infectionMember 2ChromatinEffector responsesMetabolic substratesT cell response to infectionT cells