2024
Association of CD8 T cell infiltration in the tumor microenvironment with survival outcomes in patients with metastatic renal cell carcinoma (mRCC).
Goswamy R, Yildirim A, Wei M, Liu Y, Choi Y, Brown J, Nazha B, Master V, Martini D, Carthon B, Harris W, Kucuk O, Kissick H, Hartman C, McClintock G, Vo B, Jansen C, Zhuang T, Bilen M. Association of CD8 T cell infiltration in the tumor microenvironment with survival outcomes in patients with metastatic renal cell carcinoma (mRCC). Journal Of Clinical Oncology 2024, 42: e16527-e16527. DOI: 10.1200/jco.2024.42.16_suppl.e16527.Peer-Reviewed Original ResearchCD8 T cell infiltrationMetastatic renal cell carcinomaProgression-free survivalT cell infiltrationCD8 T cellsCheckpoint inhibitorsOverall survivalTyrosine kinase inhibitorsT cellsSystemic therapyTumor microenvironmentMetastatic renal cell carcinoma patientsAssociated with favorable clinical outcomesProgression-free survival outcomesRetrospective analysis of patientsCombination checkpoint inhibitorsIntratumoral T cellsProgression free survivalImproved overall survivalFavorable clinical outcomesWinship Cancer InstituteKaplan Meier analysisAnalysis of patientsRenal cell carcinomaCox proportional hazards models
2022
Clinical outcome following checkpoint therapy in renal cell carcinoma is associated with a burst of activated CD8 T cells in blood
Carlisle J, Jansen C, Cardenas M, Sobierajska E, Reyes A, Greenwald R, Del Balzo L, Prokhnevska N, Kucuk O, Carthon B, Mullane P, Osunkoya A, Baumgarten D, Hosseinzadeh F, Wilkinson S, Lake R, Sowalsky A, Liu Y, Master V, Bilen M, Kissick H. Clinical outcome following checkpoint therapy in renal cell carcinoma is associated with a burst of activated CD8 T cells in blood. Journal For ImmunoTherapy Of Cancer 2022, 10: e004803. PMID: 35863822, PMCID: PMC9310235, DOI: 10.1136/jitc-2022-004803.Peer-Reviewed Original ResearchConceptsRenal cell carcinomaCD8 T cellsCheckpoint therapyT cellsHLA-DRCell carcinomaClinical benefitActivation markers HLA-DRAdvanced renal cell carcinomaPre-existing immune responsesImmune responsePredictor of clinical benefitPeripheral T cell activationPeripheral blood of patientsFlow cytometryT-cell receptor (TCR) sequencingIntratumoral T cellsAntitumor immune responseMarkers HLA-DRAbundant T cellsProportion of CD4Cornerstone of treatmentT cell activationBlood of patientsPredicting therapeutic responseImpact of Chemoembolic Regimen on Immune Cell Recruitment and Immune Checkpoint Marker Expression following Transcatheter Arterial Chemoembolization in a VX2 Rabbit Liver Tumor Model
Berz AM, Santana JG, Iseke S, Gross M, Pekurovsky V, Laage Gaupp F, Savic LJ, Borde T, Gottwald LA, Boustani AM, Gebauer B, Lin M, Zhang X, Schlachter T, Madoff DC, Chapiro J. Impact of Chemoembolic Regimen on Immune Cell Recruitment and Immune Checkpoint Marker Expression following Transcatheter Arterial Chemoembolization in a VX2 Rabbit Liver Tumor Model. Journal Of Vascular And Interventional Radiology 2022, 33: 764-774.e4. PMID: 35346859, PMCID: PMC9344951, DOI: 10.1016/j.jvir.2022.03.026.Peer-Reviewed Original ResearchConceptsTranscatheter arterial chemoembolizationCytotoxic T-lymphocyte-associated protein 4Rabbit liver tumor modelConventional TACEImmune checkpoint marker expressionLiver tumor modelVX2 rabbit liver tumor modelArterial chemoembolizationBicarbonate infusionImmune responseDifferentiation 3T-lymphocyte-associated protein 4Conventional transcatheter arterial chemoembolizationTumor modelCell death protein 1Marker expressionIntratumoral T cellsImmune checkpoint markersT cell infiltrationDeath protein 1Antigen-presenting cellsImmune cell recruitmentNew Zealand white rabbitsZealand white rabbitsAPC infiltration
2021
A reservoir of stem-like CD8+ T cells in the tumor-draining lymph node preserves the ongoing anti-tumor immune response
Connolly KA, Kuchroo M, Venkat A, Khatun A, Wang J, William I, Hornick NI, Fitzgerald BL, Damo M, Kasmani MY, Cui C, Fagerberg E, Monroy I, Hutchins A, Cheung JF, Foster GG, Mariuzza DL, Nader M, Zhao H, Cui W, Krishnaswamy S, Joshi NS. A reservoir of stem-like CD8+ T cells in the tumor-draining lymph node preserves the ongoing anti-tumor immune response. Science Immunology 2021, 6: eabg7836. PMID: 34597124, PMCID: PMC8593910, DOI: 10.1126/sciimmunol.abg7836.Peer-Reviewed Original ResearchConceptsTumor-specific CD8T cellsTumor microenvironmentOngoing anti-tumor immune responseChronic lymphocytic choriomeningitis virus (LCMV) infectionTumor-draining lymph nodesAnti-tumor immune responseLymphocytic choriomeningitis virus infectionIntratumoral T cellsEfficacy of immunotherapyT cell responsesTumor-draining lymphAntitumor T cellsT cell terminal differentiationStem-like CD8Immunologic shiftGene expression signaturesLymph nodesTerminal differentiationLung tumorsVirus infectionLung adenocarcinomaImmune responseCD8Cell responses5‐Fluorouracil efficacy requires anti‐tumor immunity triggered by cancer‐cell‐intrinsic STING
Tian J, Zhang D, Kurbatov V, Wang Q, Wang Y, Fang D, Wu L, Bosenberg M, Muzumdar MD, Khan S, Lu Q, Yan Q, Lu J. 5‐Fluorouracil efficacy requires anti‐tumor immunity triggered by cancer‐cell‐intrinsic STING. The EMBO Journal 2021, 40: embj2020106065. PMID: 33615517, PMCID: PMC8013832, DOI: 10.15252/embj.2020106065.Peer-Reviewed Original ResearchConceptsAnti-tumor immunityTumor burdenSubsequent type I interferon productionHigh STING expressionIntratumoral T cellsT-cell depletionType I interferon productionI interferon productionLoss of STINGImmunocompetent hostsColorectal specimensT cellsSTING expressionBetter survivalHigh doseTherapeutic effectivenessHuman colorectal specimensMelanoma tumorsInterferon productionChemotherapeutic drugsMurine colonImmunityEfficacyStingsColon
2018
A dormant TIL phenotype defines non-small cell lung carcinomas sensitive to immune checkpoint blockers
Gettinger SN, Choi J, Mani N, Sanmamed MF, Datar I, Sowell R, Du VY, Kaftan E, Goldberg S, Dong W, Zelterman D, Politi K, Kavathas P, Kaech S, Yu X, Zhao H, Schlessinger J, Lifton R, Rimm DL, Chen L, Herbst RS, Schalper KA. A dormant TIL phenotype defines non-small cell lung carcinomas sensitive to immune checkpoint blockers. Nature Communications 2018, 9: 3196. PMID: 30097571, PMCID: PMC6086912, DOI: 10.1038/s41467-018-05032-8.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAntibodies, BlockingCarcinogenesisCarcinoma, Non-Small-Cell LungCell ProliferationCytotoxicity, ImmunologicHistocompatibility Antigens Class IHumansLung NeoplasmsLymphocyte ActivationLymphocytes, Tumor-InfiltratingMaleMice, Inbred NODMice, SCIDMutant ProteinsMutationNicotianaPeptidesPhenotypeProgrammed Cell Death 1 ReceptorReproducibility of ResultsSurvival AnalysisConceptsImmune checkpoint blockersCheckpoint blockersQuantitative immunofluorescenceNon-small cell lung carcinoma patientsCell lung carcinoma patientsNon-small cell lung carcinomaPatient-derived xenograft modelsIntratumoral T cellsMultiplexed quantitative immunofluorescencePD-1 blockadeLevels of CD3Lung carcinoma patientsCell lung carcinomaT cell proliferationPre-treatment samplesTIL phenotypeSurvival benefitCarcinoma patientsEffector capacityLung carcinomaT cellsWhole-exome DNA sequencingXenograft modelFavorable responseBlockers
2010
T cell infiltrate and outcome following resection of intermediate-grade primary neuroendocrine tumours and liver metastases
Katz S, Donkor C, Glasgow K, Pillarisetty V, Gönen M, Espat N, Klimstra D, D'Angelica M, Allen P, Jarnagin W, DeMatteo R, Brennan M, Tang L. T cell infiltrate and outcome following resection of intermediate-grade primary neuroendocrine tumours and liver metastases. Hepato Pancreato Biliary 2010, 12: 674-683. PMID: 21083792, PMCID: PMC3003477, DOI: 10.1111/j.1477-2574.2010.00231.x.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overChi-Square DistributionDatabases as TopicDisease-Free SurvivalFemaleHumansImmunohistochemistryKaplan-Meier EstimateLiver NeoplasmsLymphocytes, Tumor-InfiltratingMaleMiddle AgedNeoplasm StagingNeuroendocrine TumorsNew York CityProportional Hazards ModelsRisk AssessmentRisk FactorsT-LymphocytesT-Lymphocytes, RegulatoryTime FactorsTreatment OutcomeYoung AdultConceptsIntermediate-grade neuroendocrine tumorsNET liver metastasesTumor-infiltrating lymphocytesRecurrence-free survivalT cell infiltrationNeuroendocrine tumorsT cellsLiver metastasesOverall survivalNeuroendocrine tumor liver metastasesPrimary pancreatic neuroendocrine tumorsRobust T cell infiltrationPredictor of prolonged survivalMedian follow-up timeTumor-infiltrating lymphocyte countsIntratumoral T cellsPrimary neuroendocrine tumorsNeuroendocrine tumor patientsPancreatic neuroendocrine tumorsRegulatory T cellsLog-rank testFollow-up timePredictors of outcomeShorter OSCD3+
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