2021
Immunotherapy in Cervical Cancer
Mauricio D, Zeybek B, Tymon-Rosario J, Harold J, Santin AD. Immunotherapy in Cervical Cancer. Current Oncology Reports 2021, 23: 61. PMID: 33852056, DOI: 10.1007/s11912-021-01052-8.Peer-Reviewed Original ResearchConceptsCervical cancerDifferent immune checkpoint inhibitorsPlatinum-based chemotherapy regimenTumor-infiltrating T lymphocytesPoly adenosine diphosphate ribose polymerase inhibitorsImmune checkpoint inhibitorsCombination therapy trialsCervical cancer patientsPositive cervical cancerNovel therapeutic modalitiesRibose polymerase inhibitorsAntibody-drug conjugatesCheckpoint inhibitorsChemotherapy regimenImmunotherapy studiesTherapeutic vaccinesInvestigative treatmentCancer patientsChemotherapy treatmentT lymphocytesTherapeutic modalitiesRecent FindingsThereTumor angiogenesis inhibitorTherapy trialsAngiogenesis inhibitors
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
Polymerase 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
2012
Mammaglobin B (SCGB2A1)-specific CD8+ cytotoxic T lymphocytes (CTL) are highly effective in killing autologous chemotherapy resistant ovarian cancer cells: Implications for SCGB2A1 dendritic cell-based therapeutic vaccines
Roque D, Bellone S, Betti M, Silasi D, Ratner E, Azodi M, Schwartz P, Rutherford T, Pecorelli S, Santin A. Mammaglobin B (SCGB2A1)-specific CD8+ cytotoxic T lymphocytes (CTL) are highly effective in killing autologous chemotherapy resistant ovarian cancer cells: Implications for SCGB2A1 dendritic cell-based therapeutic vaccines. Gynecologic Oncology 2012, 125: s34. DOI: 10.1016/j.ygyno.2011.12.078.Peer-Reviewed Original Research
2009
Human Papillomavirus Type 16 (HPV-16) Virus-Like Particle L1-Specific CD8+ Cytotoxic T Lymphocytes (CTLs) Are Equally Effective as E7-Specific CD8+ CTLs in Killing Autologous HPV-16-Positive Tumor Cells in Cervical Cancer Patients: Implications for L1 Dendritic Cell-Based Therapeutic Vaccines
Bellone S, El-Sahwi K, Cocco E, Casagrande F, Cargnelutti M, Palmieri M, Bignotti E, Romani C, Silasi DA, Azodi M, Schwartz PE, Rutherford TJ, Pecorelli S, Santin AD. Human Papillomavirus Type 16 (HPV-16) Virus-Like Particle L1-Specific CD8+ Cytotoxic T Lymphocytes (CTLs) Are Equally Effective as E7-Specific CD8+ CTLs in Killing Autologous HPV-16-Positive Tumor Cells in Cervical Cancer Patients: Implications for L1 Dendritic Cell-Based Therapeutic Vaccines. Journal Of Virology 2009, 83: 6779-6789. PMID: 19386711, PMCID: PMC2698533, DOI: 10.1128/jvi.02443-08.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedCancer VaccinesCapsid ProteinsCell Line, TumorDendritic CellsFemaleGene Expression ProfilingHuman papillomavirus 16HumansMiddle AgedOncogene Proteins, ViralPapillomavirus E7 ProteinsPapillomavirus InfectionsRepressor ProteinsRNA, ViralT-Lymphocytes, CytotoxicUterine Cervical NeoplasmsYoung AdultConceptsCervical cancer patientsCytotoxic T lymphocytesAutologous tumor cellsCancer patientsDendritic cellsT lymphocytesL1 VLPsCervical cancerTumor cellsE7 RNADendritic cell-based therapeutic vaccineE7-specific cytotoxic T lymphocytesHPV-16 positive cervical cancerCell-mediated immune responsesExpression levelsAutologous dendritic cellsHPV-16 VLPPromising prophylactic vaccineE7-specific CD8Human papillomavirus infectionT lymphocyte responsesStrong cytolytic activityTreatment of patientsPeripheral blood lymphocytesPrimary cervical tumors
2008
Generation of CA125-specific cytotoxic T lymphocytes in human leukocyte antigen-A2.1-positive healthy donors and patients with advanced ovarian cancer
Bellone S, Anfossi S, O'Brien TJ, Cannon MJ, Silasi DA, Azodi M, Schwartz PE, Rutherford TJ, Pecorelli S, Santin AD. Generation of CA125-specific cytotoxic T lymphocytes in human leukocyte antigen-A2.1-positive healthy donors and patients with advanced ovarian cancer. American Journal Of Obstetrics And Gynecology 2008, 200: 75.e1-75.e10. PMID: 18976739, DOI: 10.1016/j.ajog.2008.08.014.Peer-Reviewed Original ResearchConceptsPeptide-specific cytotoxic T lymphocytesCytotoxic T lymphocytesHuman leukocyte antigenLeukocyte antigenOvarian cancerT lymphocytesHuman cytotoxic T-lymphocyte responsesCytotoxic T-lymphocyte precursor frequenciesNatural killer-sensitive targetsPeptide-loaded target cellsType 1 cytokine profileCytotoxic T lymphocyte responsesT lymphocyte precursor frequenciesPotential immunogenic peptidesAdvanced ovarian cancerClass I antibodiesIntracellular cytokine expressionT lymphocyte responsesPositive healthy donorsInterferon-gamma productionT lymphocyte populationsPeripheral blood leukocytesCytokine profileELISPOT assayCytokine expression
2003
In vitro induction of tumor-specific HLA class I-restricted CD8+ cytotoxic T lymphocytes from patients with locally advanced breast cancer by tumor antigen-pulsed autologous dendritic cells11Supported in part by grants from the Arkansas Breast Cancer Research Program, the Arkansas Special Population Network (A-SPAN), and the Camillo Golgi Foundation, Brescia, Italy (to A.S.).
Kass R, Agha J, Bellone S, Palmieri M, Canè S, Bignotti E, Henry-Tillman R, Hutchins L, Cannon MJ, Klimberg S, Santin AD. In vitro induction of tumor-specific HLA class I-restricted CD8+ cytotoxic T lymphocytes from patients with locally advanced breast cancer by tumor antigen-pulsed autologous dendritic cells11Supported in part by grants from the Arkansas Breast Cancer Research Program, the Arkansas Special Population Network (A-SPAN), and the Camillo Golgi Foundation, Brescia, Italy (to A.S.). Journal Of Surgical Research 2003, 112: 189-197. PMID: 12888337, DOI: 10.1016/s0022-4804(03)00147-1.Peer-Reviewed Original ResearchConceptsAutologous tumor cellsAdvanced breast cancerHLA class IAntigen-pulsed dendritic cellsIntracellular cytokine expressionDendritic cellsBreast cancerFlow cytometric analysisTumor cellsCytokine expressionClass IT lymphocytesAutologous Epstein-Barr virus-transformed lymphoblastoid cell linesTumor antigen-pulsed dendritic cellsTumor lysate-pulsed dendritic cellsLysate-pulsed dendritic cellsPowerful antigen-presenting cellsTwo-color flow cytometric analysisCytometric analysisPeripheral blood mononuclear cellsSurface markersVirus-transformed lymphoblastoid cell linesEpstein-Barr virus-transformed lymphoblastoid cell linesColor flow cytometric analysisBreast Cancer Research Program
2000
Induction of Ovarian Tumor-Specific CD8+ Cytotoxic T Lymphocytes by Acid-Eluted Peptide-Pulsed Autologous Dendritic Cells
SANTIN A, BELLONE S, RAVAGGI A, PECORELLI S, CANNON M, PARHAM G. Induction of Ovarian Tumor-Specific CD8+ Cytotoxic T Lymphocytes by Acid-Eluted Peptide-Pulsed Autologous Dendritic Cells. Obstetrics And Gynecology 2000, 96: 422-430. DOI: 10.1097/00006250-200009000-00019.Peer-Reviewed Original ResearchConceptsAutologous tumor cellsAdvanced ovarian cancerT lymphocyte responsesCytotoxic T lymphocytesDendritic cellsT lymphocytesOvarian cancerTumor cellsLymphocyte responsesTumor-specific cytotoxic T-cell responseTumour peptide-pulsed dendritic cellsAutologous ovarian cancer cellsAutologous ovarian tumor cellsPeptide-pulsed dendritic cellsAnti-HLA class ICytotoxic T lymphocyte responsesCytotoxic T cell responsesTwo-color flow cytometric analysisPeripheral blood mononuclear cellsHLA-A2 monoclonal antibodyClass IAutologous dendritic cellsTumor-specific CD8T cell responsesStrong cytolytic activityIn vitro induction of tumor-specific human lymphocyte antigen class I–restricted CD8+ cytotoxic T lymphocytes by ovarian tumor antigen–pulsed autologous dendritic cells from patients with advanced ovarian cancer
Santin A, Hermonat P, Ravaggi A, Bellone S, Pecorelli S, Cannon M, Parham G. In vitro induction of tumor-specific human lymphocyte antigen class I–restricted CD8+ cytotoxic T lymphocytes by ovarian tumor antigen–pulsed autologous dendritic cells from patients with advanced ovarian cancer. American Journal Of Obstetrics And Gynecology 2000, 183: 601-609. PMID: 10992180, DOI: 10.1067/mob.2000.107097.Peer-Reviewed Original ResearchConceptsAutologous tumor cellsAdvanced ovarian cancerTumor lysate-pulsed dendritic cellsLysate-pulsed dendritic cellsCytotoxic T lymphocytesDendritic cellsAntigen class IT lymphocytesOvarian cancerTumor cellsAutologous Epstein-Barr virus-transformed lymphoblastoid cell linesTumor-specific cytotoxic T-cell responseAutologous ovarian cancer cellsAutologous ovarian tumor cellsHuman leukocyte antigen (HLA) class IAdvanced stage ovarian cancerCytotoxic T lymphocyte responsesClass I monoclonal antibodiesCytotoxic T cell responsesVirus-transformed lymphoblastoid cell linesEpstein-Barr virus-transformed lymphoblastoid cell linesClass IHuman lymphocyte antigen class IAutologous dendritic cellsHigh cytotoxic activityInduction of ovarian tumor-specific CD8+ cytotoxic T lymphocytes by acid-eluted peptide-pulsed autologous dendritic cells.
Santin A, Bellone S, Ravaggi A, Pecorelli S, Cannon M, Parham G. Induction of ovarian tumor-specific CD8+ cytotoxic T lymphocytes by acid-eluted peptide-pulsed autologous dendritic cells. Obstetrics And Gynecology 2000, 96: 422-30. PMID: 10960637, DOI: 10.1016/s0029-7844(00)00916-9.Peer-Reviewed Original ResearchConceptsAutologous tumor cellsAdvanced ovarian cancerPeptide-pulsed dendritic cellsT lymphocyte responsesDendritic cellsT lymphocytesOvarian cancerTumor cellsLymphocyte responsesTumor-specific cytotoxic T-cell responsePeptide-pulsed autologous dendritic cellsTumour peptide-pulsed dendritic cellsAutologous ovarian cancer cellsAutologous ovarian tumor cellsAnti-HLA class ICytotoxic T lymphocyte responsesCytotoxic T cell responsesTwo-color flow cytometric analysisPeripheral blood mononuclear cellsHLA-A2 monoclonal antibodyClass IAutologous dendritic cellsTumor-specific CD8T cell responsesStrong cytolytic activityInterleukin-10 Increases Th1 Cytokine Production and Cytotoxic Potential in Human Papillomavirus-Specific CD8+ Cytotoxic T Lymphocytes
Santin A, Hermonat P, Ravaggi A, Bellone S, Pecorelli S, Roman J, Parham G, Cannon M. Interleukin-10 Increases Th1 Cytokine Production and Cytotoxic Potential in Human Papillomavirus-Specific CD8+ Cytotoxic T Lymphocytes. Journal Of Virology 2000, 74: 4729-4737. PMID: 10775611, PMCID: PMC111995, DOI: 10.1128/jvi.74.10.4729-4737.2000.Peer-Reviewed Original ResearchMeSH KeywordsCells, CulturedCytokinesCytotoxicity, ImmunologicFemaleFlow CytometryHistocompatibility Antigens Class IHumansInterleukin-10Interleukin-2Lymphocyte ActivationMembrane GlycoproteinsPapillomaviridaePapillomavirus InfectionsPerforinPore Forming Cytotoxic ProteinsTh1 CellsT-Lymphocytes, CytotoxicTumor Cells, CulturedTumor Virus InfectionsUterine Cervical NeoplasmsConceptsIL-10IL-2Immunosuppressive cytokinesT lymphocytesSolid-phase anti-CD3 antibodyTumor necrosis factor alphaIntracellular perforin levelsTh1 cytokine secretionAutologous tumor cellsTime pointsTumor-specific CTLsTh1 cytokine productionCervical cancer patientsCytotoxic activityCytotoxic T lymphocytesNecrosis factor alphaT cell proliferationAnti-CD3 antibodyIFN-gamma expressionFluorescence-activated cell sorterGrowth factor betaIL-2 expressionLater time pointsAdoptive transfusionCD56 molecules