2022
PI3K activation allows immune evasion by promoting an inhibitory myeloid tumor microenvironment
Collins NB, Al Abosy R, Miller BC, Bi K, Zhao Q, Quigley M, Ishizuka JJ, Yates KB, Pope HW, Manguso RT, Shrestha Y, Wadsworth M, Hughes T, Shalek AK, Boehm JS, Hahn WC, Doench JG, Haining WN. PI3K activation allows immune evasion by promoting an inhibitory myeloid tumor microenvironment. Journal For ImmunoTherapy Of Cancer 2022, 10: e003402. PMID: 35264433, PMCID: PMC8915320, DOI: 10.1136/jitc-2021-003402.Peer-Reviewed Original ResearchConceptsImmune evasionCheckpoint blockadePI3K activationMouse syngeneic tumor modelsPharmacological PI3K inhibitionEfficacy of immunotherapyNumber of CD8Tumor immune evasionTumor immune microenvironmentRational combination strategiesSyngeneic tumor modelsCell-extrinsic effectsK activationPI3K inhibitionMyeloid microenvironmentImmune microenvironmentPoor responseMyeloid infiltrationT cellsImmune responseImmunotherapyMyeloid cellsImmune systemPhospho-inositol-3 kinaseTumor microenvironment
2021
Reprogramming of the esophageal squamous carcinoma epigenome by SOX2 promotes ADAR1 dependence
Wu Z, Zhou J, Zhang X, Zhang Z, Xie Y, Liu JB, Ho ZV, Panda A, Qiu X, Cejas P, Cañadas I, Akarca FG, McFarland JM, Nagaraja AK, Goss LB, Kesten N, Si L, Lim K, Liu Y, Zhang Y, Baek JY, Liu Y, Patil DT, Katz JP, Hai J, Bao C, Stachler M, Qi J, Ishizuka JJ, Nakagawa H, Rustgi AK, Wong KK, Meyerson M, Barbie DA, Brown M, Long H, Bass AJ. Reprogramming of the esophageal squamous carcinoma epigenome by SOX2 promotes ADAR1 dependence. Nature Genetics 2021, 53: 881-894. PMID: 33972779, PMCID: PMC9124436, DOI: 10.1038/s41588-021-00859-2.Peer-Reviewed Original ResearchMeSH Keywords3' Untranslated RegionsAdenosine DeaminaseAnimalsBase SequenceCarcinogenesisCell Line, TumorCell Transformation, NeoplasticCyclin-Dependent Kinase Inhibitor p16Endogenous RetrovirusesEnhancer Elements, GeneticEpigenomeEsophageal NeoplasmsEsophageal Squamous Cell CarcinomaGene Expression Regulation, NeoplasticGenome, HumanHumansInterferonsIntronsKruppel-Like Transcription FactorsMiceOrganoidsProtein BindingRNA, Double-StrandedRNA-Binding ProteinsSOXB1 Transcription FactorsTumor Suppressor Protein p53ConceptsRNA editing enzyme ADAR1Activity of oncogenesTranscription factor Sox2Chromatin remodelingSox2 bindingSOX2 activityTranscriptional landscapeEnzyme ADAR1Sox2 functionFactor Sox2Esophageal squamous cell carcinomaEsophageal organoidsTargetable vulnerabilitiesEndogenous retrovirusesSOX2Chromosome 3q amplificationSOX2 overexpressionPrecursor cellsP16 inactivationOncogeneEpigenomeCistromeNormal tissuesSquamous esophagusADAR1