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 repressionEGFR-driven lung adenocarcinomas coopt alveolar macrophage metabolism and function to support EGFR signaling and growth.
Kuhlmann-Hogan A, Cordes T, Xu Z, Kuna R, Traina K, Robles-Oteiza C, Ayeni D, Kwong E, Levy S, Globig A, Nobari M, Cheng G, Leibel S, Homer R, Shaw R, Metallo C, Politi K, Kaech S. EGFR-driven lung adenocarcinomas coopt alveolar macrophage metabolism and function to support EGFR signaling and growth. Cancer Discovery 2024, 14: 524-545. PMID: 38241033, PMCID: PMC11258210, DOI: 10.1158/2159-8290.cd-23-0434.Peer-Reviewed Original ResearchLung adenocarcinomaGM-CSFEGFR-mutant lung adenocarcinomaGM-CSF secretionProinflammatory immune responseSuppress tumor progressionLocal immunosuppressionStatin therapyTherapeutic combinationsNovel therapiesTumor cellsTumor progressionTumor growthLung adenocarcinoma cellsEGFR phosphorylationImmune responseTransformed epitheliumCancer cellsInflammatory functionsEGFR signalingMacrophage metabolismAlveolar macrophagesIncreased cholesterol synthesisMetabolic supportOncogenic signalingEGFR-Driven Lung Adenocarcinomas Co-opt Alveolar Macrophage Metabolism and Function to Support EGFR Signaling and Growth.
Kuhlmann-Hogan A, Cordes T, Xu Z, Kuna R, Traina K, Robles-Oteíza C, Ayeni D, Kwong E, Levy S, Globig A, Nobari M, Cheng G, Leibel S, Homer R, Shaw R, Metallo C, Politi K, Kaech S. EGFR-Driven Lung Adenocarcinomas Co-opt Alveolar Macrophage Metabolism and Function to Support EGFR Signaling and Growth. Cancer Discovery 2024, of1-of22. PMID: 38270272, DOI: 10.1158/2159-8290.cd-23-0434.Peer-Reviewed Original ResearchLung adenocarcinomaGM-CSFEGFR-mutant lung adenocarcinomaT cell-based immunotherapyTransformed epitheliumOncogenic signalingGM-CSF secretionProinflammatory immune responseSuppress tumor progressionLocal immunosuppressionStatin therapyTherapeutic combinationsNovel therapiesTumor cellsTumor progressionTumor growthLung cancerLung adenocarcinoma cellsEGFR phosphorylationImmune responseImmunological supportCancer cellsInflammatory functionsAlveolar macrophagesIncreased cholesterol synthesis