2014
The combination of HTATIP2 expression and microvessel density predicts converse survival of hepatocellular carcinoma with or without sorafenib
Wang W, Liu L, Xu H, Sun H, Wu C, Zhu X, Zhang W, Xu J, Liu C, Long J, Ni Q, Tang Z, Yu X. The combination of HTATIP2 expression and microvessel density predicts converse survival of hepatocellular carcinoma with or without sorafenib. Oncotarget 2014, 5: 3895-3906. PMID: 25008315, PMCID: PMC4116529, DOI: 10.18632/oncotarget.2019.Peer-Reviewed Original ResearchConceptsSurvival of hepatocellular carcinomaMicrovessel densityHepatocellular carcinomaSorafenib treatmentDissemination of hepatocellular carcinomaAssociated with inhibition of angiogenesisAdvanced hepatocellular carcinomaMicrovessel density valuesCurative HCC resectionSuppressor of tumor growthInhibition of angiogenesisNegative prognostic indicatorAssociated with inhibitionSorafenib interventionHCC resectionSorafenib administrationOverall survivalDisease recurrencePrognostic factorsTissue microarrayPrognostic indicatorTumor growthSorafenibPersonalized treatmentPredictive valueIntegrated metabolomic profiling of hepatocellular carcinoma in hepatitis C cirrhosis through GC/MS and UPLC/MS‐MS
Fitian A, Nelson D, Liu C, Xu Y, Ararat M, Cabrera R. Integrated metabolomic profiling of hepatocellular carcinoma in hepatitis C cirrhosis through GC/MS and UPLC/MS‐MS. Liver International 2014, 34: 1428-1444. PMID: 24661807, PMCID: PMC4169337, DOI: 10.1111/liv.12541.Peer-Reviewed Original ResearchMeSH Keywords12-Hydroxy-5,8,10,14-eicosatetraenoic AcidAmino AcidsBile Acids and SaltsCarcinoma, HepatocellularChromatography, High Pressure LiquidDicarboxylic AcidsGas Chromatography-Mass SpectrometryHepatitis CHumansHydroxyeicosatetraenoic AcidsLiver CirrhosisLiver NeoplasmsMetabolomeMetabolomicsMultivariate AnalysisROC CurveSphingosineTandem Mass SpectrometryXanthineConceptsPresence of HCCHepatocellular carcinomaUPLC/MS-MSHCC patientsMetabolic alterationsHepatitis C cirrhosisBile acid metabolismHallmarks of HCCMetabolomic profilingAcid metabolismReceiver operator characteristic analysisOperator characteristic analysisGlobal metabolic alterationsMetabolic pathway disturbancesC cirrhosisHCV cirrhosisHepatitis CMetabolic disturbancesHCC developmentSerum metabolomeHealthy volunteersEicosanoid pathwayCirrhosisPathway disturbancesBile acids
2013
Linking metabolism and epigenetic regulation in development of hepatocellular carcinoma
Puszyk W, Le Trinh T, Chapple S, Liu C. Linking metabolism and epigenetic regulation in development of hepatocellular carcinoma. Laboratory Investigation 2013, 93: 983-990. PMID: 23917878, PMCID: PMC4028619, DOI: 10.1038/labinvest.2013.94.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarcinoma, HepatocellularDNA MethylationEpigenomicsHumansLiver NeoplasmsMetabolomeMicroRNAsConceptsHepatocellular carcinomaLate-stage hepatocellular carcinomaDevelopment of HCCAltered liver metabolismHepatitis B virusMajor risk factorProgression of HCCHepatitis CLiver functionB virusMicro RNA expressionRisk factorsLiver metabolismMetabolic organSurvival rateCancerRNA expressionCommon formCarcinomaUnderlying metabolic processesLiverExogenous environmental factorsEnvironmental factorsExcessive consumptionExposureEpigenetic Upregulation of HGF and c-Met Drives Metastasis in Hepatocellular Carcinoma
Ogunwobi O, Puszyk W, Dong H, Liu C. Epigenetic Upregulation of HGF and c-Met Drives Metastasis in Hepatocellular Carcinoma. PLOS ONE 2013, 8: e63765. PMID: 23723997, PMCID: PMC3665785, DOI: 10.1371/journal.pone.0063765.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBase SequenceCarcinogenesisCarcinoma, HepatocellularCell Line, TumorDNA MethylationEpigenesis, GeneticEpithelial-Mesenchymal TransitionGene Expression Regulation, NeoplasticHepatocyte Growth FactorHumansLiver NeoplasmsMesodermMiceMice, Inbred BALB CModels, BiologicalMolecular Sequence DataNeoplastic Cells, CirculatingPromoter Regions, GeneticProto-Oncogene Proteins c-metUp-RegulationConceptsEpithelial-mesenchymal transitionHepatocyte growth factorExpression of HGFHepatocellular carcinomaC-MetHematogenous disseminationTumor cellsRole of HGFOrthotopic syngeneic modelsMetastatic hepatocellular carcinomaMouse HCC modelC-Met expressionUpregulation of HGFPrimary tumor cellsPromoter demethylationNovel non-invasive approachPotential clinical applicationsPeripheral bloodSyngeneic modelHCC managementDrives metastasisEpigenetic upregulationHCC modelTumor progressionMetastatic potential
2012
Immune modulation of effector CD4+ and regulatory T cell function by sorafenib in patients with hepatocellular carcinoma
Cabrera R, Ararat M, Xu Y, Brusko T, Wasserfall C, Atkinson M, Chang L, Liu C, Nelson D. Immune modulation of effector CD4+ and regulatory T cell function by sorafenib in patients with hepatocellular carcinoma. Cancer Immunology, Immunotherapy 2012, 62: 737-746. PMID: 23223899, PMCID: PMC3863727, DOI: 10.1007/s00262-012-1380-8.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic AgentsCarcinoma, HepatocellularCase-Control StudiesCD4-Positive T-LymphocytesCoculture TechniquesCytokinesDose-Response Relationship, ImmunologicEnzyme-Linked Immunosorbent AssayHumansInterleukin-2 Receptor alpha SubunitLiver NeoplasmsNiacinamidePhenylurea CompoundsSorafenibT-Lymphocytes, RegulatoryConceptsEffect of sorafenibHepatocellular carcinomaTeff activationT cellsLow dosesTeff responsesTumor immunityRegulatory T cell functionImpact of sorafenibEffector T cellsRegulatory T cellsTreg suppressive functionPeripheral mononuclear cellsCD25 surface expressionT cell functionNovel combination treatmentTreg suppressionEffector CD4Treg functionPharmacologic dosesTeff proliferationImmune reactivitySystemic drugsCD25 expressionMononuclear cellsGuardian and Selective Killer: The Versatile Functions of TLR3 in Hepatocellular Carcinoma
Liu C. Guardian and Selective Killer: The Versatile Functions of TLR3 in Hepatocellular Carcinoma. Journal Of The National Cancer Institute 2012, 104: 1780-1782. PMID: 23197496, PMCID: PMC3514168, DOI: 10.1093/jnci/djs475.Peer-Reviewed Original ResearchOPA1 downregulation is involved in sorafenib-induced apoptosis in hepatocellular carcinoma
Zhao X, Tian C, Puszyk W, Ogunwobi O, Cao M, Wang T, Cabrera R, Nelson D, Liu C. OPA1 downregulation is involved in sorafenib-induced apoptosis in hepatocellular carcinoma. Laboratory Investigation 2012, 93: 8-19. PMID: 23108376, PMCID: PMC3860369, DOI: 10.1038/labinvest.2012.144.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisCarcinoma, HepatocellularCell Line, TumorCytochromes cDown-RegulationGene Knockdown TechniquesGTP PhosphohydrolasesHumansLiverLiver NeoplasmsMiceMice, SCIDMitochondriaNiacinamidePhenylurea CompoundsPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktRaf KinasesRas ProteinsRNA, Small InterferingSignal TransductionSorafenibXenograft Model Antitumor AssaysConceptsHepatocellular carcinomaSorafenib-induced apoptosisHCC xenograft tumor growthOptic atrophy 1HCC cellsPatients' hepatocellular carcinomaNon-tumor tissue samplesAdvanced hepatocellular carcinomaPathogenesis of HCCNovel therapeutic targetTumorigenesis of HCCXenograft tumor growthTumor tissue analysisNormal human primary hepatocytesHuman primary hepatocytesCell growth inhibitionSorafenib treatmentHCC patientsTherapeutic targetExposure of cellsTumor growthMitochondrial injuryPatientsSorafenibOPA1 expressionNanoparticle-based artificial RNA silencing machinery for antiviral therapy
Wang Z, Liu H, Yang S, Wang T, Liu C, Cao Y. Nanoparticle-based artificial RNA silencing machinery for antiviral therapy. Proceedings Of The National Academy Of Sciences Of The United States Of America 2012, 109: 12387-12392. PMID: 22802676, PMCID: PMC3412013, DOI: 10.1073/pnas.1207766109.Peer-Reviewed Original ResearchConceptsFundamental gene regulatory mechanismsHepatitis C virusGene regulatory mechanismsCultured cellsTarget RNA cleavageSequence-specific mannerCellular interferon responseFunctional genomicsHuman hepatoma cellsRNA interferenceArtificial RNARegulatory mechanismsMouse modelRNA cleavageCultured human hepatoma cellsSpecific mannerHCV RNA levelsRNAXenotransplantation mouse modelHepatoma cellsInterferon responsePotent antiviral activityRNA levelsMachineryProteinase activityTargeted Delivery of Chemotherapy Agents Using a Liver Cancer-Specific Aptamer
Meng L, Yang L, Zhao X, Zhang L, Zhu H, Liu C, Tan W. Targeted Delivery of Chemotherapy Agents Using a Liver Cancer-Specific Aptamer. PLOS ONE 2012, 7: e33434. PMID: 22558072, PMCID: PMC3338807, DOI: 10.1371/journal.pone.0033434.Peer-Reviewed Original ResearchConceptsAptamer-drug conjugatesCancer-specific aptamersAntitumor agent doxorubicinDOX conjugatesIntercalation methodAptamerCell viability testTargeted deliveryConjugatesCancer cellsTarget proteinsAgent doxorubicinPotential candidateCell linesDOXEfficiency of chemotherapyLiver cancer cellsNonspecific uptakeTarget specificityAvailable aptamersCarcinoma cell linesChemotherapy agentsHepatocellular carcinoma cell linesHuman hepatocellular carcinoma cell linePromising methodCyclooxygenase‐2 and Akt mediate multiple growth‐factor‐induced epithelial‐mesenchymal transition in human hepatocellular carcinoma
Ogunwobi O, Wang T, Zhang L, Liu C. Cyclooxygenase‐2 and Akt mediate multiple growth‐factor‐induced epithelial‐mesenchymal transition in human hepatocellular carcinoma. Journal Of Gastroenterology And Hepatology 2012, 27: 566-578. PMID: 22097969, PMCID: PMC3288221, DOI: 10.1111/j.1440-1746.2011.06980.x.Peer-Reviewed Original ResearchMeSH KeywordsAlbuminsAlpha 1-AntitrypsinAnimalsCadherinsCarcinoma, HepatocellularCell MovementCell TransplantationCollagen Type ICyclooxygenase 2DinoprostoneEpidermal Growth FactorEpithelial-Mesenchymal TransitionFibroblast Growth Factor 2FibronectinsGene ExpressionHepatocyte Growth FactorHumansMiceOncogene Protein v-aktRNA, Small InterferingSignal TransductionTransforming Growth Factor beta1Tumor Cells, CulturedVimentinConceptsEpithelial-mesenchymal transitionCyclooxygenase-2Hepatocellular carcinomaBasic fibroblast growth factorGrowth factorProstaglandin E2Metastatic hepatocellular carcinomaProgression of HCCEffective therapeutic strategyExpression of vimentinHepatocyte growth factorGrowth factor βHuman hepatocellular carcinomaFibroblast growth factorAssociated hepatitisChemopreventive strategiesEpidermal growth factorMultiple growth factorsTherapeutic strategiesMesenchymal changesSignificant mortalityAkt pathwayMolecular targetingCancer invasionAkt
2011
Therapeutic and prognostic importance of epithelial–mesenchymal transition in liver cancers: Insights from experimental models
Ogunwobi O, Liu C. Therapeutic and prognostic importance of epithelial–mesenchymal transition in liver cancers: Insights from experimental models. Critical Reviews In Oncology/Hematology 2011, 83: 319-328. PMID: 22178416, DOI: 10.1016/j.critrevonc.2011.11.007.Peer-Reviewed Original ResearchConceptsEpithelial-mesenchymal transitionHepatocellular carcinomaHepatic metastasesPrognostic importanceExperimental modelColon cancerTreatment of patientsRole of EMTHuman cancer patientsPotential therapeutic targetHuman malignant diseaseSignificant morbidityCancer patientsMalignant diseaseMalignant conditionsLiver cancerTherapeutic targetBasic scientistsCancerFurther studiesPatientsCarcinomaMetastasisLiverHuman tissuesSurvivin Inhibition Is Critical for Bcl-2 Inhibitor-Induced Apoptosis in Hepatocellular Carcinoma Cells
Zhao X, Ogunwobi O, Liu C. Survivin Inhibition Is Critical for Bcl-2 Inhibitor-Induced Apoptosis in Hepatocellular Carcinoma Cells. PLOS ONE 2011, 6: e21980. PMID: 21829603, PMCID: PMC3148218, DOI: 10.1371/journal.pone.0021980.Peer-Reviewed Original ResearchConceptsBcl-2 inhibitorsCombination treatmentHCC cellsABT-263Survivin inhibitionHepatocellular carcinomaHuman liver cancer tissuesSingle treatmentFuture clinical trialsApoptotic effectsLiver cancer tissuesLiver cancer therapyERK activationHCC cell linesHepatocellular carcinoma cellsPreclinical dataClinical trialsTherapeutic effectLow doseNormal human hepatocytesCancer tissuesYM-155High dosesNovel Bcl-2 inhibitorABT-263-induced apoptosisDevelopment of optimized AAV3 serotype vectors: mechanism of high-efficiency transduction of human liver cancer cells
Cheng B, Ling C, Dai Y, Lu Y, Glushakova L, Gee S, McGoogan K, Aslanidi G, Park M, Stacpoole P, Siemann D, Liu C, Srivastava A, Ling C. Development of optimized AAV3 serotype vectors: mechanism of high-efficiency transduction of human liver cancer cells. Gene Therapy 2011, 19: 375-384. PMID: 21776025, PMCID: PMC3519243, DOI: 10.1038/gt.2011.105.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBreast NeoplasmsCarcinoma, HepatocellularCell Line, TumorDependovirusFemaleGenetic VectorsHumansLiver NeoplasmsMiceMutagenesis, Site-DirectedProteasome InhibitorsProtein Structure, TertiaryProto-Oncogene Proteins c-metTransduction, GeneticTransplantation, HeterologousTyrosineVirus IntegrationConceptsHigh-efficiency transductionAAV3 vectorsTransduction efficiencySerotype vectorsSurface-exposed tyrosinePotential gene therapyHuman hepatocyte growth factor receptorHuman liver cancer cellsGene therapyLiver cancer cellsTransgene expressionVector entryAAV3 capsidsDirect intratumoral injectionAAV3Tail vein injectionLiver tumor cellsIntratumoral injectionCancer cellsEfficiencyAdenoVectorIntracellular kinase domainVirus serotypesHepatocyte growth factor upregulation promotes carcinogenesis and epithelial-mesenchymal transition in hepatocellular carcinoma via Akt and COX-2 pathways
Ogunwobi O, Liu C. Hepatocyte growth factor upregulation promotes carcinogenesis and epithelial-mesenchymal transition in hepatocellular carcinoma via Akt and COX-2 pathways. Clinical & Experimental Metastasis 2011, 28: 721-731. PMID: 21744257, PMCID: PMC3732749, DOI: 10.1007/s10585-011-9404-x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlotting, WesternCadherinsCarcinoma, HepatocellularCell AdhesionCell DifferentiationCell Line, TumorCell MovementCell ProliferationCyclooxygenase 2Enzyme-Linked Immunosorbent AssayEpithelial-Mesenchymal TransitionExtracellular Signal-Regulated MAP KinasesHepatocyte Growth FactorLiver Neoplasms, ExperimentalMiceMice, Inbred BALB CNeoplasm InvasivenessPhosphorylationProto-Oncogene Proteins c-aktReverse Transcriptase Polymerase Chain ReactionRNA, MessengerSignal TransductionUp-RegulationVimentinConceptsEpithelial-mesenchymal transitionHepatocyte growth factorCyclooxygenase-2Hepatocellular carcinomaBNL cellsMarkers of EMTDevelopment of HCCAdvanced hepatocellular carcinomaCOX-2 pathwayMetastatic hepatocellular carcinomaUpregulation of HGFMesenchymal characteristicsGrowth factor upregulationE-cadherinCharacteristic epithelial morphologyCancer mortalitySubsequent metastasisEMT markersImportant causeMigratory capacityHCC cellsBNL CLCancer progressionCollagen 1Growth factorKinase inhibitor Sorafenib modulates immunosuppressive cell populations in a murine liver cancer model
Cao M, Xu Y, Youn J, Cabrera R, Zhang X, Gabrilovich D, Nelson D, Liu C. Kinase inhibitor Sorafenib modulates immunosuppressive cell populations in a murine liver cancer model. Laboratory Investigation 2011, 91: 598-608. PMID: 21321535, PMCID: PMC3711234, DOI: 10.1038/labinvest.2010.205.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBenzenesulfonatesBone Marrow CellsCarcinoma, HepatocellularCell DivisionCell Line, TumorDisease ProgressionImmunity, CellularLiver NeoplasmsMiceMice, Inbred BALB CMyeloid CellsNiacinamidePhenylurea CompoundsProtein Kinase InhibitorsPyridinesSorafenibSpleenT-Lymphocytes, RegulatoryConceptsMyeloid-derived suppressor cellsImmunosuppressive cell populationsAnti-tumor immunityTumor-bearing hostsImmune cell populationsLiver cancer modelMurine liver cancer modelHepatocellular carcinomaCell populationsCancer modelNovel multi-kinase inhibitorSuppressive immune cell populationBALB/c miceDepletion of TregsImpact of sorafenibRegulatory T cellsAdvanced hepatocellular carcinomaTreatment of sorafenibKinase inhibitor sorafenibMulti-kinase inhibitorHCC cell growthSuppressor cellsTumor burdenC miceCancer patientsReactive Oxygen Species Is Essential for Cycloheximide to Sensitize Lexatumumab-Induced Apoptosis in Hepatocellular Carcinoma Cells
Zhao X, Cao M, Liu J, Zhu H, Nelson D, Liu C. Reactive Oxygen Species Is Essential for Cycloheximide to Sensitize Lexatumumab-Induced Apoptosis in Hepatocellular Carcinoma Cells. PLOS ONE 2011, 6: e16966. PMID: 21347335, PMCID: PMC3037406, DOI: 10.1371/journal.pone.0016966.Peer-Reviewed Original ResearchAntibodies, MonoclonalApoptosisBcl-2 Homologous Antagonist-Killer ProteinBcl-2-Associated X ProteinCarcinoma, HepatocellularCaspasesCell Line, TumorCycloheximideDrug InteractionsGene Expression Regulation, NeoplasticHSP90 Heat-Shock ProteinsHumansIntracellular SpaceLiver NeoplasmsReactive Oxygen SpeciesDNA Methylation Suppresses Expression of the Urea Cycle Enzyme Carbamoyl Phosphate Synthetase 1 (CPS1) in Human Hepatocellular Carcinoma
Liu H, Dong H, Robertson K, Liu C. DNA Methylation Suppresses Expression of the Urea Cycle Enzyme Carbamoyl Phosphate Synthetase 1 (CPS1) in Human Hepatocellular Carcinoma. American Journal Of Pathology 2011, 178: 652-661. PMID: 21281797, PMCID: PMC3069978, DOI: 10.1016/j.ajpath.2010.10.023.Peer-Reviewed Original ResearchMeSH KeywordsCarbamoyl-Phosphate Synthase (Ammonia)Carcinoma, HepatocellularCell Line, TumorCpG IslandsDNA MethylationGene Expression Regulation, EnzymologicGene Expression Regulation, NeoplasticHepatocyte Nuclear Factor 3-betaHepatocytesHumansLiver NeoplasmsPromoter Regions, GeneticQuaternary Ammonium CompoundsRNA, MessengerUreaConceptsHCC cellsNoncancerous tissuesTumor tissueHepatocyte paraffin 1 antibodySurgical pathology practiceLiver cancer tissuesHuman HCC cellsCPS1 expressionHCC tumor tissuesLiver tumor tissuesHuman hepatocellular carcinomaHuman hepatocellular carcinoma cellsCultured human primary hepatocytesHuman primary hepatocytesHepatocellular carcinoma cellsHepatocellular carcinomaCPS1 geneRate-limiting enzymeLiver carcinogenesisCancer tissuesSynthetase 1Potential biomarkersCarbamoyl phosphate synthetase 1Pathology practiceCarcinoma cells
2010
Different radiosensitivity of CD4+CD25+ regulatory T cells and effector T cells to low dose gamma irradiation in vitro
Cao M, Cabrera R, Xu Y, Liu C, Nelson D. Different radiosensitivity of CD4+CD25+ regulatory T cells and effector T cells to low dose gamma irradiation in vitro. International Journal Of Radiation Biology 2010, 87: 71-80. PMID: 20958220, PMCID: PMC3806980, DOI: 10.3109/09553002.2010.518208.Peer-Reviewed Original ResearchMeSH KeywordsAgedApoptosisBcl-2-Associated X ProteinCarcinoma, HepatocellularCaspase 3Cell ProliferationDose-Response Relationship, RadiationFas ReceptorFemaleGamma RaysHumansIn Vitro TechniquesInterferon-gammaInterleukin-10Liver NeoplasmsMaleMiddle AgedRadiation ToleranceT-Lymphocyte SubsetsT-Lymphocytes, RegulatoryConceptsEffector T cellsAdvanced hepatocellular carcinomaRegulatory T cellsT cellsHepatocellular carcinomaLow-dose gamma raysLow-dose irradiationApoptosis-related proteinsImmune responseLow dosesEnhanced immune responseCaspase-3Dose-dependent reductionB-cell lymphoma 2X protein expressionCell lymphoma 2Interleukin-10Peripheral bloodActive caspase-3Low-dose gamma irradiationCytokine secretionTregsLuminex assaysBlood samplesInduction of apoptosisInfluence of Serum and Soluble CD25 (sCD25) on Regulatory and Effector T‐cell Function in Hepatocellular Carcinoma
Cabrera R, Ararat M, Eksioglu E, Cao M, Xu Y, Wasserfall C, Atkinson M, Liu C, Nelson D. Influence of Serum and Soluble CD25 (sCD25) on Regulatory and Effector T‐cell Function in Hepatocellular Carcinoma. Scandinavian Journal Of Immunology 2010, 72: 293-301. PMID: 20883314, PMCID: PMC2951624, DOI: 10.1111/j.1365-3083.2010.02427.x.Peer-Reviewed Original ResearchConceptsHepatocellular carcinomaHCC serumSerum-free mediumSoluble CD25Pg/Effector T cell responsesEffector T cell functionSerum-mediated suppressionRegulatory T cellsT cell responsesSera of patientsT cell functionHealthy control cellsNovel therapeutic targetDose-dependent fashionCD25 cell surface expressionTeff responsesTreg suppressionInfluence of serumCirrhosis patientsTeff proliferationTumor burdenCD25 expressionCell surface expressionPoor survival
2009
Hepatocellular Carcinoma Immunopathogenesis: Clinical Evidence for Global T Cell Defects and an Immunomodulatory Role for Soluble CD25 (sCD25)
Cabrera R, Ararat M, Cao M, Xu Y, Wasserfall C, Atkinson M, Liu C, Nelson D. Hepatocellular Carcinoma Immunopathogenesis: Clinical Evidence for Global T Cell Defects and an Immunomodulatory Role for Soluble CD25 (sCD25). Digestive Diseases And Sciences 2009, 55: 484-495. PMID: 19714465, PMCID: PMC3161029, DOI: 10.1007/s10620-009-0955-5.Peer-Reviewed Original ResearchConceptsT cell responsesHCC patientsHepatocellular carcinomaCell responsesTumor burdenImpaired T cell responsesLower IFN-γ productionEffector T cell responsesIL-2 receptor alpha chainATP production assaysLevels of sCD25Tolerogenic tumor environmentIFN-γ ELISPOTEffector T cellsT cell immunityT cell reactivityIFN-γ productionIL-2 supplementationT cell defectsDose-dependent mannerReceptor alpha chainIL-2 signalingSerum sCD25Soluble CD25Worse survival