Hypoxia is linked to acquired resistance to immune checkpoint inhibitors in lung cancer
Robles-Oteíza C, Hastings K, Choi J, Sirois I, Ravi A, Expósito F, de Miguel F, Knight J, López-Giráldez F, Choi H, Socci N, Merghoub T, Awad M, Getz G, Gainor J, Hellmann M, Caron É, Kaech S, Politi K. Hypoxia is linked to acquired resistance to immune checkpoint inhibitors in lung cancer. Journal Of Experimental Medicine 2024, 222: e20231106. PMID: 39585348, DOI: 10.1084/jem.20231106.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsNon-small cell lung cancerAcquired resistanceCheckpoint inhibitorsResistant tumorsPatients treated with anti-PD-1/PD-L1 therapyAnti-PD-1/PD-L1 therapyLung cancerResistance to immune checkpoint inhibitorsAssociated with decreased progression-free survivalHypoxia activated pro-drugsTargeting hypoxic tumor regionsTreat non-small cell lung cancerAnti-CTLA-4Anti-PD-1Immune checkpoint inhibitionTumor metabolic featuresProgression-free survivalCell lung cancerResistant cancer cellsHypoxic tumor regionsMHC-II levelsRegions of hypoxiaKnock-outCheckpoint inhibitionTranscriptional 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 repression