2020
Neoantigen-based EpiGVAX vaccine initiates antitumor immunity in colorectal cancer
Kim VM, Pan X, Soares KC, Azad NS, Ahuja N, Gamper CJ, Blair AB, Muth S, Ding D, Ladle BH, Zheng L. Neoantigen-based EpiGVAX vaccine initiates antitumor immunity in colorectal cancer. JCI Insight 2020, 5: e136368. PMID: 32376802, PMCID: PMC7253020, DOI: 10.1172/jci.insight.136368.Peer-Reviewed Original ResearchConceptsMetastatic colorectal cancerColorectal cancerDNA methyltransferase inhibitorAntitumor efficacyAntigen-specific antitumor immune responsesAntitumor T-cell responsesCancer testis antigen expressionAntitumor immune responseT cell responsesAntitumor immunityCancer vaccinesSurvival outcomesCombination therapyAntigen expressionImmune responseMurine modelCTA expressionCell responsesNeoantigensImproved efficacyTumor cellsVaccineEfficacyGVAXMethyltransferase inhibitor
2019
Expression of PD-1 by T Cells in Malignant Glioma Patients Reflects Exhaustion and Activation
Davidson T, Lee A, Hsu M, Sedighim S, Orpilla J, Treger J, Mastall M, Roesch S, Rapp C, Galvez M, Mochizuki A, Antonios J, Garcia A, Kotecha N, Bayless N, Nathanson D, Wang A, Everson R, Yong W, Cloughesy T, Liau L, Herold-Mende C, Prins R. Expression of PD-1 by T Cells in Malignant Glioma Patients Reflects Exhaustion and Activation. Clinical Cancer Research 2019, 25: 1913-1922. PMID: 30498094, PMCID: PMC6420851, DOI: 10.1158/1078-0432.ccr-18-1176.Peer-Reviewed Original ResearchConceptsPD-1<sup>+</sup> T cellsTumor-infiltrating lymphocytesPD-1<sup>+</sup> tumor-infiltrating lymphocytesPD-1 expressionPD-1T cellsPD-1<sup>+</supMalignant gliomasT lymphocytesEffective antitumor T-cell responsesExpression of markers of activationAntitumor T-cell responsesPD-1 blocking therapyExpression of PD-1Peripheral blood T lymphocytesExpressed PD-1PD-1/PD-L1T cell responsesBlood T lymphocytesIncreased proliferative capacityMarkers of activationPrimary malignant tumorHuman T lymphocytesHallmarks of memoryCentral nervous system
2018
Differential regulation of PD-L1 expression by immune and tumor cells in NSCLC and the response to treatment with atezolizumab (anti–PD-L1)
Kowanetz M, Zou W, Gettinger SN, Koeppen H, Kockx M, Schmid P, Kadel EE, Wistuba I, Chaft J, Rizvi NA, Spigel DR, Spira A, Hirsch FR, Cohen V, Smith D, Boyd Z, Miley N, Flynn S, Leveque V, Shames DS, Ballinger M, Mocci S, Shankar G, Funke R, Hampton G, Sandler A, Amler L, Mellman I, Chen DS, Hegde PS. Differential regulation of PD-L1 expression by immune and tumor cells in NSCLC and the response to treatment with atezolizumab (anti–PD-L1). Proceedings Of The National Academy Of Sciences Of The United States Of America 2018, 115: e10119-e10126. PMID: 30297397, PMCID: PMC6205493, DOI: 10.1073/pnas.1802166115.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerPD-L1 expressionImmune cellsTumor cellsCases of NSCLCHigh PD-L1 expressionHigh PD-L1 levelsSingle-agent checkpoint inhibitorsAntitumor T-cell responsesTumor-infiltrating immune cellsPD-L1 levelsEffector T cellsTumor-infiltrating lymphocytesDurable clinical responsesPD-L1 geneT cell responsesCell lung cancerStratification of patientsPoor immune infiltrationCheckpoint inhibitorsClinical responseAnticancer immunityImmune infiltrationLung cancerDesmoplastic stromaSENP3 maintains the stability and function of regulatory T cells via BACH2 deSUMOylation
Yu X, Lao Y, Teng XL, Li S, Zhou Y, Wang F, Guo X, Deng S, Chang Y, Wu X, Liu Z, Chen L, Lu LM, Cheng J, Li B, Su B, Jiang J, Li HB, Huang C, Yi J, Zou Q. SENP3 maintains the stability and function of regulatory T cells via BACH2 deSUMOylation. Nature Communications 2018, 9: 3157. PMID: 30089837, PMCID: PMC6082899, DOI: 10.1038/s41467-018-05676-6.Peer-Reviewed Original ResearchMeSH KeywordsActive Transport, Cell NucleusAnimalsAntineoplastic AgentsAutoimmunityBasic-Leucine Zipper Transcription FactorsBone Marrow CellsCD4-Positive T-LymphocytesCell DifferentiationCell Line, TumorCell NucleusCysteine EndopeptidasesFemaleGene DeletionGene Expression ProfilingGene Expression RegulationHEK293 CellsHomeostasisHumansImmune ToleranceLymphocyte ActivationMelanoma, ExperimentalMiceMice, Inbred C57BLMice, KnockoutPeptide HydrolasesReactive Oxygen SpeciesSumoylationT-Lymphocytes, RegulatoryConceptsRegulatory T cellsTreg cellsT cellsReactive oxygen speciesSUMO-specific protease 3T effector cell differentiationAntitumor T-cell responsesTreg cell-specific deletionT cell responsesEffector cell differentiationTreg cell stabilityCell-specific deletionT cell activationImmune toleranceTumor immunosuppressionAutoimmune symptomsImmune homeostasisRegulation of ROSRole of SENP3Cell activationCell responsesGene signatureProtease 3Pivotal regulatorNuclear export
2017
Stat6 Promotes Intestinal Tumorigenesis in a Mouse Model of Adenomatous Polyposis by Expansion of MDSCs and Inhibition of Cytotoxic CD8 Response
Jayakumar A, Bothwell ALM. Stat6 Promotes Intestinal Tumorigenesis in a Mouse Model of Adenomatous Polyposis by Expansion of MDSCs and Inhibition of Cytotoxic CD8 Response. Neoplasia 2017, 19: 595-605. PMID: 28654863, PMCID: PMC5487300, DOI: 10.1016/j.neo.2017.04.006.Peer-Reviewed Original ResearchMeSH KeywordsAdenomatous Polyposis ColiAnimalsBecaplerminBiomarkersCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCell Transformation, NeoplasticCytotoxicity, ImmunologicDisease Models, AnimalDisease ProgressionGene DeletionGene ExpressionInterleukin-4Intestinal MucosaIntestine, SmallMiceMice, KnockoutMyeloid-Derived Suppressor CellsProgrammed Cell Death 1 ReceptorProto-Oncogene Proteins c-sisSTAT6 Transcription FactorConceptsIntestinal tumorigenesisIL-4-induced STAT6Tumor-promoting growth factorsAntitumor T-cell responsesHuman colorectal cancer tissuesMore CD8 cellsPD-1 expressionEpithelial cellsExpansion of MDSCsT cell responsesIL-4 expressionCell proliferationColorectal cancer tissuesPlatelet-derived growth factor-BBIntestinal tumor progressionIntestinal epithelial cellsGrowth factor-BBColon cancer cell linesCD8 responsesPolyp progressionStrong CD8Cancer cell linesCD4 cellsCD8 cellsImmunosuppressive mediators
2014
Blockade of the B7-H1/PD-1 Pathway as a Basis for Combination Anticancer Therapy
Sznol M. Blockade of the B7-H1/PD-1 Pathway as a Basis for Combination Anticancer Therapy. The Cancer Journal 2014, 20: 290-295. PMID: 25098290, DOI: 10.1097/ppo.0000000000000056.Peer-Reviewed Original ResearchConceptsPD-1/PD-L1 blockadePD-L1 blockadeT cell responsesTumor-specific T-cell responsesB7-H1/PDCell responsesOverall risk-benefit ratioAntitumor T-cell responsesTumor microenvironmentAnimal tumor model systemsAbundant preclinical dataAutoimmune-like toxicitiesSubset of patientsRecent clinical trialsRisk-benefit ratioT lymphocyte suppressionEarly clinical developmentActivated T lymphocytesTumor model systemsCombination anticancer therapyClinical responseDurable responsesDeath-1Metastatic melanomaPreclinical data
2011
Tumor-Associated Antigen Expressing Listeria monocytogenes Induces Effective Primary and Memory T-Cell Responses Against Hepatic Colorectal Cancer Metastases
Olino K, Wada S, Edil BH, Pan X, Meckel K, Weber W, Slansky J, Tamada K, Lauer P, Brockstedt D, Pardoll D, Schulick R, Yoshimura K. Tumor-Associated Antigen Expressing Listeria monocytogenes Induces Effective Primary and Memory T-Cell Responses Against Hepatic Colorectal Cancer Metastases. Annals Of Surgical Oncology 2011, 19: 597-607. PMID: 21979110, PMCID: PMC4498288, DOI: 10.1245/s10434-011-2037-0.Peer-Reviewed Original ResearchMeSH KeywordsAnalysis of VarianceAnimalsAntigens, DifferentiationAntigens, NeoplasmAntineoplastic Agents, AlkylatingCarcinomaCD8-Positive T-LymphocytesCell Line, TumorColonic NeoplasmsCTLA-4 AntigenCyclophosphamideFemaleImmunotherapyInterferon-gammaListeria monocytogenesLiver NeoplasmsLymphocyte CountMiceMice, Inbred BALB CProgrammed Cell Death 1 ReceptorStatistics, NonparametricSurvival AnalysisT-Lymphocytes, RegulatoryConceptsT cell responsesEffector memory T cellsMetastatic colorectal cancerMemory T cellsTumor rechallengeColorectal cancerT cellsTumor-specific T-cell responsesAntigen-specific effector CD8Tumor-specific cytotoxic CD8Antitumor T-cell responsesEffective antitumor T-cell responsesMemory T cell responsesHepatic colorectal cancer metastasesCurrent immunotherapeutic strategiesImmune checkpoint moleculesColorectal cancer metastasisCTLA-4 expressionTumor-associated antigensTumor associated antigensCT26 colon cancer cell lineL. monocytogenes strainsColon cancer cell linesImmunologic milieuCancer cell lines
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