2024
Randomized Phase II Trial of Imiquimod with or without 9-Valent HPV Vaccine versus Observation in Patients with High-grade Pre-neoplastic Cervical Lesions (NCT02864147)
Sheth S, Oh J, Bellone S, Siegel E, Greenman M, Mutlu L, McNamara B, Pathy S, Clark M, Azodi M, Altwerger G, Andikyan V, Huang G, Ratner E, Kim D, Iwasaki A, Levi A, Buza N, Hui P, Flaherty S, Schwartz P, Santin A. Randomized Phase II Trial of Imiquimod with or without 9-Valent HPV Vaccine versus Observation in Patients with High-grade Pre-neoplastic Cervical Lesions (NCT02864147). Clinical Cancer Research 2024, 30: of1-of10. PMID: 38592381, DOI: 10.1158/1078-0432.ccr-23-3639.Peer-Reviewed Original ResearchConceptsRandomized phase II trialCD4/CD8 T cellsT cellsHPV clearanceArm BNo significant differenceClinical surveillanceRate of HPV clearanceSecondary outcomesPre-neoplastic cervical lesionsCervical intraepithelial neoplasiaT cell infiltrationT cell responsesSignificant differenceCIN3 patientsIntraepithelial neoplasiaArm ACervical lesionsImiquimod groupSurveillance armVaginal suppositoriesProspective trialsArm CHPV vaccinationImiquimod
2022
Distinct Mechanisms of Mismatch-Repair Deficiency Delineate Two Modes of Response to Anti-PD-1 Immunotherapy in Endometrial Carcinoma.
Chow RD, Michaels T, Bellone S, Hartwich T, Bonazzoli E, Iwasaki A, Song E, Santin AD. Distinct Mechanisms of Mismatch-Repair Deficiency Delineate Two Modes of Response to Anti-PD-1 Immunotherapy in Endometrial Carcinoma. Cancer Discovery 2022, 13: 312-331. PMID: 36301137, PMCID: PMC9905265, DOI: 10.1158/2159-8290.cd-22-0686.Peer-Reviewed Original ResearchConceptsAnti-PD-1 immunotherapyImmune checkpoint blockadeMMRd tumorsNK cellsEndometrial carcinomaICB responseMutation burdenT-cell-driven immunityPhase II clinical trialMMRd endometrial cancersPD-1 inhibitorsMismatch repair-deficient cancersTumor-extrinsic factorsHigh response rateEffector CD8Antitumor immunityEndometrial cancerCancer immunotherapyImmune cellsLonger survivalClinical trialsPrimary resistanceT cellsResponse rateMMRd
2004
Restoration of tumor specific human leukocyte antigens class I-restricted cytotoxicity by dendritic cell stimulation of tumor infiltrating lymphocytes in patients with advanced ovarian cancer
Santin A, Bellone S, Palmieri M, Bossini B, Cane' S, Bignotti E, Roman J, Cannon M, Pecorelli S. Restoration of tumor specific human leukocyte antigens class I-restricted cytotoxicity by dendritic cell stimulation of tumor infiltrating lymphocytes in patients with advanced ovarian cancer. International Journal Of Gynecological Cancer 2004, 14: 64-75. DOI: 10.1136/ijgc-00009577-200401000-00008.Peer-Reviewed Original ResearchPeripheral blood lymphocytesAdvanced ovarian cancerAdvanced ovarian cancer patientsDendritic cellsOvarian cancer patientsOvarian cancerT cellsCancer patientsClass ILymphoblastoid cell linesTumor antigen-loaded dendritic cellsTumor lysate-pulsed dendritic cellsTumor-specific T-cell responsesAutologous ovarian cancer cellsAutologous tumor target cellsDC stimulationLysate-pulsed dendritic cellsType 1 cytokine biasAntigen-loaded dendritic cellsAnti-HLA class IAutologous Epstein-Barr virusSpecific human leukocyte antigenProfessional antigen presenting cellsAdoptive T-cell immunotherapyAutologous tumor cellsRestoration of tumor specific human leukocyte antigens class I‐restricted cytotoxicity by dendritic cell stimulation of tumor infiltrating lymphocytes in patients with advanced ovarian cancer
Santin AD, Bellone S, Palmieri M, Bossini B, Cane' S, Bignotti E, Roman JJ, Cannon MJ, Pecorelli S. Restoration of tumor specific human leukocyte antigens class I‐restricted cytotoxicity by dendritic cell stimulation of tumor infiltrating lymphocytes in patients with advanced ovarian cancer. International Journal Of Gynecological Cancer 2004, 14: 64-75. PMID: 14764031, DOI: 10.1111/j.1048-891x.2004.014175.x.Peer-Reviewed Original ResearchConceptsPeripheral blood lymphocytesAdvanced ovarian cancerAdvanced ovarian cancer patientsDendritic cellsOvarian cancer patientsOvarian cancerT cellsCancer patientsClass ILymphoblastoid cell linesTumor antigen-loaded dendritic cellsTumor lysate-pulsed dendritic cellsTumor-specific T-cell responsesAutologous ovarian cancer cellsAutologous tumor target cellsDC stimulationLysate-pulsed dendritic cellsType 1 cytokine biasAntigen-loaded dendritic cellsAnti-HLA class IAutologous Epstein-Barr virusIFN-gamma-positive cellsSpecific human leukocyte antigenProfessional antigen presenting cellsAdoptive T-cell immunotherapy
2002
Induction of tumour-specific CD8+ cytotoxic T lymphocytes by tumour lysate-pulsed autologous dendritic cells in patients with uterine serous papillary cancer
Santin AD, Bellone S, Ravaggi A, Roman JJ, Pecorelli S, Parham GP, Cannon MJ. Induction of tumour-specific CD8+ cytotoxic T lymphocytes by tumour lysate-pulsed autologous dendritic cells in patients with uterine serous papillary cancer. British Journal Of Cancer 2002, 86: 151-157. PMID: 11857027, PMCID: PMC2746546, DOI: 10.1038/sj.bjc.6600026.Peer-Reviewed Original ResearchConceptsAutologous tumor cellsUterine serous papillary cancerAutologous dendritic cellsT cellsPatient 1Patient 3Tumor cellsDendritic cellsPapillary cancerOvarian cancerAutologous tumor target cellsTumor lysate-pulsed DCsAnti-HLA class IUterine serous papillary carcinomaColor flow cytometric analysisCancer-specific CD8Cisplatinum-based chemotherapyLumboaortic lymph nodesPapillary cancer patientsTumor-specific toleranceTumor-specific CD8Intracellular cytokine expressionHigh-grade ovarian cancerT lymphocyte responsesStrong cytolytic activity
2001
Phenotypic and Functional Analysis of Tumor-Infiltrating Lymphocytes Compared with Tumor-Associated Lymphocytes from Ascitic Fluid and Peripheral Blood Lymphocytes in Patients with Advanced Ovarian Cancer
Santin AD, Hermonat PL, Ravaggi A, Bellone S, Roman JJ, Smith CV, Pecorelli S, Radominska-Pandya A, Cannon MJ, Parham GP. Phenotypic and Functional Analysis of Tumor-Infiltrating Lymphocytes Compared with Tumor-Associated Lymphocytes from Ascitic Fluid and Peripheral Blood Lymphocytes in Patients with Advanced Ovarian Cancer. Gynecologic And Obstetric Investigation 2001, 51: 254-261. PMID: 11408737, DOI: 10.1159/000058060.Peer-Reviewed Original ResearchConceptsTumor-associated lymphocytesTumor-infiltrating lymphocytesPeripheral blood lymphocytesAdvanced ovarian cancerType 1 cytokinesT cellsBlood lymphocytesOvarian cancerAscitic fluidAntigen-experienced T lymphocytesActivation markers HLA-DREarly activation markers CD25Markers HLA-DRType 2 cytokinesActivation markers CD25Major leukocyte populationsIL-2 pathwayIL-2 receptorFunction of lymphocytesIL-2 productionLow surface expressionLymphocyte subsetsHigher proportionHLA-DRActivation markersTumor-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
2000
Effects of concurrent cisplatinum administration during radiotherapy vs. radiotherapy alone on the immune function of patients with cancer of the uterine cervix
Santin A, Hermonat P, Ravaggi A, Bellone S, Roman J, Pecorelli S, Cannon M, Parham G. Effects of concurrent cisplatinum administration during radiotherapy vs. radiotherapy alone on the immune function of patients with cancer of the uterine cervix. International Journal Of Radiation Oncology • Biology • Physics 2000, 48: 997-1006. PMID: 11072156, DOI: 10.1016/s0360-3016(00)00769-0.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic AgentsCisplatinCombined Modality TherapyFemaleHumansImmunity, CellularInterferon-gammaInterleukin-2Killer Cells, NaturalLymphocyte ActivationLymphocyte SubsetsMembrane GlycoproteinsMiddle AgedPerforinPore Forming Cytotoxic ProteinsProspective StudiesReceptors, Interleukin-2Uterine Cervical NeoplasmsConceptsT cellsIL-2Lymphoblast transformationRadiation therapyImmune functionNatural killer cytotoxic activityCD25-positive lymphocytesRadiation-induced immunosuppressionPercentage of CD8Advanced cervical cancerT cell numbersNatural killer cellsT cell subsetsActivation markers CD25C-RTMean absolute numberB cell numbersK562 cellsCisplatinum administrationConcurrent cisplatinumLymphocyte subsetsNK cellsConcurrent administrationKiller cellsUterine cervixDevelopment and Therapeutic Effect of Adoptively Transferred T Cells Primed by Tumor Lysate-Pulsed Autologous Dendritic Cells in a Patient with Metastatic Endometrial Cancer
Santin AD, Hermonat PL, Ravaggi A, Bellone S, Cowan C, Coke C, Pecorelli S, Cannon MJ, Parham GP. Development and Therapeutic Effect of Adoptively Transferred T Cells Primed by Tumor Lysate-Pulsed Autologous Dendritic Cells in a Patient with Metastatic Endometrial Cancer. Gynecologic And Obstetric Investigation 2000, 49: 194-203. PMID: 10729762, DOI: 10.1159/000010246.Peer-Reviewed Original ResearchMeSH KeywordsAgedCD56 AntigenCD8-Positive T-LymphocytesCombined Modality TherapyDendritic CellsEndometrial NeoplasmsFemaleFlow CytometryHepatic ArteryHistocompatibility Antigens Class IHumansImmunophenotypingImmunotherapy, AdoptiveLiver NeoplasmsL-Lactate DehydrogenaseT-LymphocytesTomography, X-Ray ComputedUric AcidConceptsAutologous dendritic cellsDendritic cellsT cellsLiver metastasesEndometrial cancerAutologous Epstein-Barr virus-transformed lymphoblastoid cellsNK-sensitive K562 cellsSerial gamma camera imagingType 1 cytokine biasTumor-specific T cellsTwo-color flow cytometric analysisPeripheral blood T cellsLarge liver metastasesMetastatic endometrial cancerAutologous tumor cellsTumor-specific CD8T cell responsesEpstein-Barr virus-transformed lymphoblastoid cellsSerum uric acidIntracellular IFN-gammaBlood T cellsLactate dehydrogenaseT-cell immunotherapyLarge tumor massSerial time pointsDevelopment, characterization and distribution of adoptively transferred peripheral blood lymphocytes primed by human papillomavirus 18 E7--pulsed autologous dendritic cells in a patient with metastatic adenocarcinoma of the uterine cervix.
Santin AD, Hermonat PL, Ravaggi A, Bellone S, Cowan C, Korourian S, Pecorelli S, Cannon MJ, Parham GP. Development, characterization and distribution of adoptively transferred peripheral blood lymphocytes primed by human papillomavirus 18 E7--pulsed autologous dendritic cells in a patient with metastatic adenocarcinoma of the uterine cervix. European Journal Of Gynaecological Oncology 2000, 21: 17-23. PMID: 10726612.Peer-Reviewed Original ResearchConceptsPeripheral blood mononuclear cellsAutologous dendritic cellsDendritic cellsT cellsMetastatic diseaseUterine cervixAutologous Epstein-Barr virus-transformed lymphoblastoid cellsNK-sensitive K562 cellsSerial gamma camera imagingTumor-specific T cellsTwo-color flow cytometric analysisPeripheral blood T cellsTumor cellsIntracellular cytokine productionAutologous tumor cellsExtensive metastatic diseaseInvasive cervical cancerTumor-specific CTLsIntracellular cytokine expressionEpstein-Barr virus-transformed lymphoblastoid cellsBlood mononuclear cellsTreatment of patientsBlood T cellsCytotoxic T cellsPeripheral blood lymphocytes