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
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