2024
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 inhibitionACLY 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
2014
The Transcription Factor FoxO1 Sustains Expression of the Inhibitory Receptor PD-1 and Survival of Antiviral CD8+ T Cells during Chronic Infection
Staron MM, Gray SM, Marshall HD, Parish IA, Chen JH, Perry CJ, Cui G, Li MO, Kaech SM. The Transcription Factor FoxO1 Sustains Expression of the Inhibitory Receptor PD-1 and Survival of Antiviral CD8+ T Cells during Chronic Infection. Immunity 2014, 41: 802-814. PMID: 25464856, PMCID: PMC4270830, DOI: 10.1016/j.immuni.2014.10.013.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, BlockingAntibodies, MonoclonalCD28 AntigensCD8-Positive T-LymphocytesCell DifferentiationCell Line, TumorChronic DiseaseForkhead Box Protein O1Forkhead Transcription FactorsGranzymesHumansInterferon-gammaJurkat CellsLymphocyte ActivationLymphocytic ChoriomeningitisLymphocytic choriomeningitis virusMiceMice, Inbred C57BLMice, TransgenicProgrammed Cell Death 1 ReceptorProto-Oncogene Proteins c-aktReceptors, Antigen, T-CellSirolimusT-Lymphocytes, CytotoxicTOR Serine-Threonine KinasesConceptsChronic viral infectionsVirus-specific CTLPD-1Viral infectionMurine lymphocytic choriomeningitis virus infectionInhibitory receptor PD-1Lymphocytic choriomeningitis virus infectionCell death protein 1Receptor PD-1Death protein 1MTOR inhibitor rapamycinExhausted CTLsAntiviral CD8Activation of AktInhibitory receptorsTranscription factor FOXO1Chronic infectionT cellsT lymphocytesTherapeutic effectVirus infectionPersistent infectionPositive feedback pathwayInfectionCTLCD4+ T Cell Help Guides Formation of CD103+ Lung-Resident Memory CD8+ T Cells during Influenza Viral Infection
Laidlaw BJ, Zhang N, Marshall HD, Staron MM, Guan T, Hu Y, Cauley LS, Craft J, Kaech SM. CD4+ T Cell Help Guides Formation of CD103+ Lung-Resident Memory CD8+ T Cells during Influenza Viral Infection. Immunity 2014, 41: 633-645. PMID: 25308332, PMCID: PMC4324721, DOI: 10.1016/j.immuni.2014.09.007.Peer-Reviewed Original ResearchConceptsT cellsTRM cellsT-betTissue-resident memory T cellsLung-resident memory CD8T cell-dependent signalsT cell-derived interferonTranscription factor T-betLung Trm cellsMemory T cellsInfluenza viral infectionInfluenza virus infectionT cell helpHeterosubtypic challengeCD103 expressionMemory CD8Respiratory infectionsMucosal sitesCell helpAirway epitheliumVirus infectionViral infectionInfectionLung airwaysImpaired abilityChronic viral infection promotes sustained Th1-derived immunoregulatory IL-10 via BLIMP-1
Parish IA, Marshall HD, Staron MM, Lang PA, Brüstle A, Chen JH, Cui W, Tsui YC, Perry C, Laidlaw BJ, Ohashi PS, Weaver CT, Kaech SM. Chronic viral infection promotes sustained Th1-derived immunoregulatory IL-10 via BLIMP-1. Journal Of Clinical Investigation 2014, 124: 3455-3468. PMID: 25003188, PMCID: PMC4109559, DOI: 10.1172/jci66108.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsChronic DiseaseCytokinesInflammation MediatorsInterleukin-10Lymphocytic ChoriomeningitisLymphocytic choriomeningitis virusMAP Kinase Signaling SystemMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicPositive Regulatory Domain I-Binding Factor 1Receptors, Antigen, T-CellTh1 CellsT-Lymphocyte SubsetsTranscription FactorsConceptsChronic viral infectionsIL-10 expressionT cell responsesIL-10 productionIL-10Th1 cellsViral infectionT cellsBlimp-1Viral-specific T cell responsesChronic lymphocytic choriomeningitis virus (LCMV) infectionAntiviral T cell responsesCell responsesImmunosuppressive cytokine IL-10Virus-specific T cellsLymphocytic choriomeningitis virus infectionChronic LCMV infectionImmunoregulatory IL-10Relevant cellular sourceCytokine IL-10Effector T cellsLCMV-infected micePersistent viral infectionT cell compartmentT cell function