2016
Polymerase ε (POLE) ultra-mutation in uterine tumors correlates with T lymphocyte infiltration and increased resistance to platinum-based chemotherapy in vitro
Bellone S, Bignotti E, Lonardi S, Ferrari F, Centritto F, Masserdotti A, Pettinella F, Black J, Menderes G, Altwerger G, Hui P, Lopez S, de Haydu C, Bonazzoli E, Predolini F, Zammataro L, Cocco E, Ferrari F, Ravaggi A, Romani C, Facchetti F, Sartori E, Odicino FE, Silasi DA, Litkouhi B, Ratner E, Azodi M, Schwartz PE, Santin AD. Polymerase ε (POLE) ultra-mutation in uterine tumors correlates with T lymphocyte infiltration and increased resistance to platinum-based chemotherapy in vitro. Gynecologic Oncology 2016, 144: 146-152. PMID: 27894751, PMCID: PMC5183545, DOI: 10.1016/j.ygyno.2016.11.023.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic AgentsCarboplatinCarcinomaCD4 Lymphocyte CountCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCell SurvivalDisease-Free SurvivalDNA Polymerase IIDrug Resistance, NeoplasmEndometrial NeoplasmsFemaleHumansMicrosatellite InstabilityMiddle AgedMutationPoly-ADP-Ribose Binding ProteinsTumor Cells, CulturedConceptsBetter prognosisTumor cell linesInfiltration of CD4Number of CD4Platinum-based chemotherapyT lymphocyte infiltrationPD-1 receptorCell linesLow metastatic capabilityPOLE-mutated tumorsWild-type ECsEC cell linesLymphocyte infiltrationFavorable prognosisPD-1EC patientsType tumorsEnhanced immunogenicityT lymphocytesMolecular subtypesTumors correlatesChemotherapyMetastatic capabilityPrognosisTumors
2015
Solitomab, an EpCAM/CD3 bispecific antibody construct (BiTE), is highly active against primary uterine serous papillary carcinoma cell lines in vitro
Bellone S, Black J, English DP, Schwab CL, Lopez S, Cocco E, Bonazzoli E, Predolini F, Ferrari F, Ratner E, Silasi DA, Azodi M, Schwartz PE, Santin AD. Solitomab, an EpCAM/CD3 bispecific antibody construct (BiTE), is highly active against primary uterine serous papillary carcinoma cell lines in vitro. American Journal Of Obstetrics And Gynecology 2015, 214: 99.e1-99.e8. PMID: 26272866, PMCID: PMC4698047, DOI: 10.1016/j.ajog.2015.08.011.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, BispecificAntigens, NeoplasmAntineoplastic AgentsAscitic FluidCarcinoma, PapillaryCD3 ComplexCD4-Positive T-LymphocytesCell Adhesion MoleculesCell Line, TumorCell ProliferationCell SurvivalCoculture TechniquesCytokinesCytotoxicity, ImmunologicEpithelial Cell Adhesion MoleculeFemaleFlow CytometryHumansLymphocyte ActivationNeoplasms, Cystic, Mucinous, and SerousT-Lymphocytes, CytotoxicUterine NeoplasmsConceptsUterine serous carcinoma cell linesUterine serous carcinomaEpithelial cell adhesion moleculeCell adhesion molecule expressionCarcinoma cell linesChromium release assaysSerous carcinoma cellsPeripheral blood lymphocytesAdhesion molecule expressionCell adhesion moleculeEpithelial cell adhesion molecule (EpCAM) expressionSerous carcinomaAdhesion moleculesBlood lymphocytesMolecule expressionT cellsAscitic fluidCell linesTumor-associated T cellsT cell-mediated killingT-cell activation markersFlow cytometryTumor cellsCarcinoma cellsRobust immunologic responsesPolymerase ε (POLE) ultra-mutated tumors induce robust tumor-specific CD4+ T cell responses in endometrial cancer patients
Bellone S, Centritto F, Black J, Schwab C, English D, Cocco E, Lopez S, Bonazzoli E, Predolini F, Ferrari F, Silasi DA, Ratner E, Azodi M, Schwartz PE, Santin AD. Polymerase ε (POLE) ultra-mutated tumors induce robust tumor-specific CD4+ T cell responses in endometrial cancer patients. Gynecologic Oncology 2015, 138: 11-17. PMID: 25931171, PMCID: PMC4469551, DOI: 10.1016/j.ygyno.2015.04.027.Peer-Reviewed Original ResearchConceptsCytotoxic T lymphocytesCancer patientsPole tumorsT cellsHigher IFN-γ expressionLevels of CD8Endometrial cancer patientsTumor-specific CD4T cell responsesEndometrial cancer cellsIFN-γ expressionHelper armCTL responsesEndometrial cancerFavorable prognosisBetter prognosisEndometrial carcinomaLymphoid subsetsNaïve CD4T lymphocytesTumor extractsCD4CD8Immune systemCell responses
2007
Human Papillomavirus Type 16 and 18 E7-Pulsed Dendritic Cell Vaccination of Stage IB or IIA Cervical Cancer Patients: a Phase I Escalating-Dose Trial
Santin AD, Bellone S, Palmieri M, Zanolini A, Ravaggi A, Siegel ER, Roman JJ, Pecorelli S, Cannon MJ. Human Papillomavirus Type 16 and 18 E7-Pulsed Dendritic Cell Vaccination of Stage IB or IIA Cervical Cancer Patients: a Phase I Escalating-Dose Trial. Journal Of Virology 2007, 82: 1968-1979. PMID: 18057249, PMCID: PMC2258728, DOI: 10.1128/jvi.02343-07.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, ViralAntibody FormationCancer VaccinesCarcinomaCD4-Positive T-LymphocytesDendritic CellsDNA-Binding ProteinsEnzyme-Linked Immunosorbent AssayFemaleHemocyaninsHumansImmunity, CellularNeoplasm StagingOncogene Proteins, ViralPapillomavirus E7 ProteinsPapillomavirus VaccinesRecombinant ProteinsUterine Cervical NeoplasmsVaccinationConceptsCervical cancer patientsIIA cervical cancer patientsDendritic cell vaccinationHuman papillomavirus type 16Cancer patientsDC vaccinationStage IBPapillomavirus type 16Cell vaccinationE7 antigenType 16Delayed-type hypersensitivity reactionEnzyme-linked immunosorbent spotHPV E7 antigenLimited tumor burdenT-cell countsEvidence of diseaseIIA cervical cancerT cell responsesKeyhole limpet hemocyaninEnzyme-linked immunosorbentHPV16/18 E7Vaccine doseAutologous DCsDTH response
2005
Definition of an Immunogenic Region Within the Ovarian Tumor Antigen Stratum Corneum Chymotryptic Enzyme
Bondurant KL, Crew MD, Santin AD, O'Brien TJ, Cannon MJ. Definition of an Immunogenic Region Within the Ovarian Tumor Antigen Stratum Corneum Chymotryptic Enzyme. Clinical Cancer Research 2005, 11: 3446-3454. PMID: 15867247, DOI: 10.1158/1078-0432.ccr-04-2043.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAntigens, NeoplasmCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCell Line, TumorCytotoxicity Tests, ImmunologicCytotoxicity, ImmunologicDendritic CellsFemaleHLA-A2 AntigenHumansImmunodominant EpitopesInterferon-gammaInterleukin-4K562 CellsKallikreinsMolecular Sequence DataOvarian NeoplasmsPeptide FragmentsProtein BindingSerine EndopeptidasesT-Lymphocytes, CytotoxicConceptsSerine protease stratum corneum chymotryptic enzymeOvarian tumor cellsHelper T-cell epitopesAntigen-specific CD4T cell responsesDendritic cellsHLA-A2.1T cell epitopesCTL responsesCell epitopesTumor cellsCTL epitopesStratum corneum chymotryptic enzymeCell responsesPeptide-loaded dendritic cellsTumor antigen-specific CD8Helper T cell responsesT helper cell epitopesAntigen-specific CD8Attractive target antigenLevel of lysisDominant CD8Multiple CD8Chymotryptic enzymeHLA-DR
2002
Effect of blood transfusion during radiotherapy on the immune function of patients with cancer of the uterine cervix: role of interleukin-10
Santin AD, Bellone S, Palmieri M, Bossini B, Dunn D, Roman JJ, Pecorelli S, Cannon M, Parham GP. Effect of blood transfusion during radiotherapy on the immune function of patients with cancer of the uterine cervix: role of interleukin-10. International Journal Of Radiation Oncology • Biology • Physics 2002, 54: 1345-1355. PMID: 12459356, DOI: 10.1016/s0360-3016(02)03757-4.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntigens, CD19Blood TransfusionB-LymphocytesCD3 ComplexCD4-Positive T-LymphocytesCD56 AntigenCD8-Positive T-LymphocytesCytokinesFemaleFlow CytometryHumansImmunophenotypingInterleukin-10Killer Cells, NaturalLymphocyte SubsetsMembrane GlycoproteinsMiddle AgedPerforinPore Forming Cytotoxic ProteinsRadiotherapyReceptors, IgGReceptors, Interleukin-2Time FactorsUterine Cervical NeoplasmsConceptsBlood transfusionT cellsUntransfused groupIL-10Transfused groupNK cellsUntransfused patientsCervical cancerIL-2Immune functionB cellsElevated serum IL-10NK-sensitive target KCD4/CD8 ratioImmunoregulatory cytokine IL-10Depression of NKIncrease of CD8Perforin-positive CD8Radiation-induced immunosuppressionPercentage of CD4Serum IL-10HLA-DR expressionNK cell cytotoxicityNumber of CD8Advanced cervical cancer
2001
Tumor-Infiltrating Lymphocytes Contain Higher Numbers of Type 1 Cytokine Expressors and DR+ T Cells Compared with Lymphocytes from Tumor Draining Lymph Nodes and Peripheral Blood in Patients with Cancer of the Uterine Cervix
Santin A, Ravaggi A, Bellone S, Pecorelli S, Cannon M, Parham G, Hermonat P. Tumor-Infiltrating Lymphocytes Contain Higher Numbers of Type 1 Cytokine Expressors and DR+ T Cells Compared with Lymphocytes from Tumor Draining Lymph Nodes and Peripheral Blood in Patients with Cancer of the Uterine Cervix. Gynecologic Oncology 2001, 81: 424-432. PMID: 11371133, DOI: 10.1006/gyno.2001.6200.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdultAgedCarcinoma, Squamous CellCD4-CD8 RatioCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCytokinesFemaleHLA-DR AntigensHumansImmunophenotypingInterferon-gammaInterleukin-2Interleukin-4Lymph NodesLymphocytesLymphocytes, Tumor-InfiltratingMiddle AgedNeoplasm StagingReceptors, Interleukin-2Th1 CellsTh2 CellsUterine Cervical NeoplasmsConceptsType 1 cytokinesLymph nodesPeripheral bloodT cellsTumor tissueLymphocyte subsetsStage IB-IIA cervical cancerAntigen-experienced T lymphocytesIB-IIA cervical cancerTumor draining lymph nodeActivation markers HLA-DREarly activation markers CD25Draining Lymph NodesMarkers HLA-DRType 2 cytokinesCervical cancer patientsRegional lymph nodesActivation markers CD25Tumor-Infiltrating LymphocytesMajor leukocyte populationsFunction of lymphocytesCervical tumor tissuesDifferent anatomical sitesHLA-DRUterine cervix
1999
Induction of Human Papillomavirus-Specific CD4+ and CD8+ Lymphocytes by E7-Pulsed Autologous Dendritic Cells in Patients with Human Papillomavirus Type 16- and 18-Positive Cervical Cancer
Santin A, Hermonat P, Ravaggi A, Chiriva-Internati M, Zhan D, Pecorelli S, Parham G, Cannon M. Induction of Human Papillomavirus-Specific CD4+ and CD8+ Lymphocytes by E7-Pulsed Autologous Dendritic Cells in Patients with Human Papillomavirus Type 16- and 18-Positive Cervical Cancer. Journal Of Virology 1999, 73: 5402-5410. PMID: 10364287, PMCID: PMC112596, DOI: 10.1128/jvi.73.7.5402-5410.1999.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaCarcinoma, Squamous CellCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCell DivisionDendritic CellsDNA-Binding ProteinsFemaleHistocompatibility TestingHLA-A AntigensHLA-B AntigensHLA-C AntigensHumansImmunophenotypingInterferon-gammaInterleukin-4Intracellular FluidK562 CellsOncogene Proteins, ViralPapillomaviridaePapillomavirus E7 ProteinsPapillomavirus InfectionsT-Lymphocytes, CytotoxicTumor Cells, CulturedTumor Virus InfectionsUterine Cervical NeoplasmsConceptsAutologous dendritic cellsAutologous tumor cellsDendritic cellsHuman papillomavirus type 16Cervical cancerLymphoblastoid cell linesPapillomavirus type 16HPV 16CTL populationsT cellsType 16Autologous Epstein-Barr virus-transformed lymphoblastoid cell linesAnti-HLA class II antibodiesAutologous tumor target cellsAnti-HLA class ICytotoxic T lymphocyte responsesTwo-color flow cytometric analysisVirus-transformed lymphoblastoid cell linesEpstein-Barr virus-transformed lymphoblastoid cell linesT cell proliferative responsesTumor cellsPotential tumor-specific targetClass II antibodiesIntracellular cytokine expressionT lymphocyte responses