2021
Epigenetic silencing by SETDB1 suppresses tumour intrinsic immunogenicity
Griffin GK, Wu J, Iracheta-Vellve A, Patti JC, Hsu J, Davis T, Dele-Oni D, Du PP, Halawi AG, Ishizuka JJ, Kim SY, Klaeger S, Knudsen NH, Miller BC, Nguyen TH, Olander KE, Papanastasiou M, Rachimi S, Robitschek EJ, Schneider EM, Yeary MD, Zimmer MD, Jaffe JD, Carr SA, Doench JG, Haining WN, Yates KB, Manguso RT, Bernstein BE. Epigenetic silencing by SETDB1 suppresses tumour intrinsic immunogenicity. Nature 2021, 595: 309-314. PMID: 33953401, PMCID: PMC9166167, DOI: 10.1038/s41586-021-03520-4.Peer-Reviewed Original ResearchConceptsImmune checkpoint blockadeCheckpoint blockadeCytotoxic T cell responsesT cell responsesMouse tumor modelsImmune exclusionImmune clustersRetroviral antigensImmune sensitivityImmunostimulatory genesIntrinsic immunogenicityCell responsesTumor modelCentral mechanismsHuman tumorsCancer cellsBlockadeCandidate targetsImmunogenicity
2019
Subsets of exhausted CD8+ T cells differentially mediate tumor control and respond to checkpoint blockade
Miller BC, Sen DR, Al Abosy R, Bi K, Virkud YV, LaFleur MW, Yates KB, Lako A, Felt K, Naik GS, Manos M, Gjini E, Kuchroo JR, Ishizuka JJ, Collier JL, Griffin GK, Maleri S, Comstock DE, Weiss SA, Brown FD, Panda A, Zimmer MD, Manguso RT, Hodi FS, Rodig SJ, Sharpe AH, Haining WN. Subsets of exhausted CD8+ T cells differentially mediate tumor control and respond to checkpoint blockade. Nature Immunology 2019, 20: 326-336. PMID: 30778252, PMCID: PMC6673650, DOI: 10.1038/s41590-019-0312-6.Peer-Reviewed Original ResearchConceptsTumor-infiltrating lymphocytesExhausted tumor-infiltrating lymphocytesT cell dysfunctionExhausted CD8T cellsCheckpoint blockadeCell dysfunctionAnti-PD-1 therapyInhibitory receptor PD-1Chronic viral infectionsExhausted T cellsReceptor PD-1Checkpoint blockade therapyDysfunctional CD8PD-1Antibody blockadeTumor controlSuch therapyCD8Viral infectionTumor growthExhausted cellsSpecific subpopulationsBlockadeTherapy
2018
Loss of ADAR1 in tumours overcomes resistance to immune checkpoint blockade
Ishizuka JJ, Manguso RT, Cheruiyot CK, Bi K, Panda A, Iracheta-Vellve A, Miller BC, Du PP, Yates KB, Dubrot J, Buchumenski I, Comstock DE, Brown FD, Ayer A, Kohnle IC, Pope HW, Zimmer MD, Sen DR, Lane-Reticker SK, Robitschek EJ, Griffin GK, Collins NB, Long AH, Doench JG, Kozono D, Levanon EY, Haining WN. Loss of ADAR1 in tumours overcomes resistance to immune checkpoint blockade. Nature 2018, 565: 43-48. PMID: 30559380, PMCID: PMC7241251, DOI: 10.1038/s41586-018-0768-9.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine DeaminaseAnimalsCell Cycle CheckpointsCell Line, TumorCRISPR-Cas SystemsDrug Resistance, NeoplasmFemaleHistocompatibility Antigens Class IImmunotherapyInflammationInterferon-Induced Helicase, IFIH1InterferonsMelanoma, ExperimentalMiceMice, Inbred C57BLPhenotypeProgrammed Cell Death 1 ReceptorReceptors, G-Protein-CoupledRNA EditingRNA, Double-StrandedRNA-Binding ProteinsConceptsImmune checkpoint blockadeCheckpoint blockadeAntigen presentationEffective anti-tumor immunityPD-1 checkpoint blockadeTumor cellsAnti-tumor immunityT cell recognitionSufficient inflammationImmunotherapy resistanceInhibitory checkpointsMost patientsInnate ligandsLoss of functionBlockadeTherapeutic requirementsLoss of ADAR1TumorsCancer cellsCell recognitionInflammationGrowth inhibitionADAR1PresentationCells