42 results on '"Francesca Rini"'
Search Results
2. Immune landscape and in vivo immunogenicity of NY-ESO-1 tumor antigen in advanced neuroblastoma patients
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Chiara Camisaschi, Salvatore Lorenzo Renne, Valeria Beretta, Francesca Rini, Rosalin Dolores Spagnuolo, Alessandra Tuccitto, Marta Giorgia Podda, Giorgio Parmiani, Licia Rivoltini, Paola Collini, Chiara Castelli, and Roberto Luksch
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Neuroblastoma ,NY-ESO-1 ,Vaccination ,Immune-checkpoints ,Immune-contexture ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Indirect evidence suggesting the immunosensitivity/immunogenicity of neuroblastoma is accumulating. The aims of this study were to investigate the immune landscape of neuroblastoma and to evaluate the in vivo immunogenicity of the NY-ESO-1 tumor antigen in advanced neuroblastoma patients. Methods The immune infiltrating cells of the NY-ESO-1+ tumors from three HLA*A201 patients with metastatic neuroblastoma who relapsed after conventional treatments were evaluated by immunohistochemistry. The patients were vaccinated with the HLA-A*0201-restricted peptide NY-ESO-1157-165(V). The peptide was emulsified in Montanide ISA51 and given subcutaneously in a phase I pilot study. The immunogenicity of NY-ESO-1 antigen was evaluated by monitoring mononuclear cells in patient peripheral blood, pre- and post-vaccine, by short-term in vitro sensitization, HLA-multimer staining and IFN-γ ELISpot analysis. Results Both CD3 T cells and CD163 myeloid cells were present in pre-vaccine tumors and PD-1 and PD-L1 expression was mainly found in the immune infiltrate. Despite the advanced stage of the disease, the vaccination induced systemic NY-ESO-1 specific CD8 T cells releasing IFN-γ in response to activation with the NY-ESO-1 peptide and an HLA-A2 positive neuroblastoma cell line. Conclusions Our results indicate that vaccination with a tumor-associated peptide is able to boost NY-ESO-1-specific, functionally active T cells in advanced neuroblastoma patients with lymphocyte infiltration in their pre-vaccine tumors. Trial registration EudraCT #2006–002859-33.
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- 2018
- Full Text
- View/download PDF
3. Melanoma Stem Cell Sphere Formation Assay
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Alessandra Tuccitto, Valeria Beretta, Francesca Rini, Chiara Castelli, and Michela Perego
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Biology (General) ,QH301-705.5 - Abstract
Self-renewal is the ability of cells to replicate themselves at every cell cycle. Throughout self-renewal in normal tissue homeostasis, stem cell number is maintained constant throughout life. Cancer stem cells (CSCs) share this ability with normal tissue stem cells and the sphere formation assay (SFA) is the gold standard assay to assess stem cells (or cancer stem cells) self-renewal potential in vitro. When single cells are plated at low density in stem cell culture medium, only the cells endowed with self-renewal are able to grow in tridimensional clusters usually named spheres. In the recent years, SFA has also been used also to test the effect of several drugs, chemical and natural compounds or microenviromental components on stem cells self-renewal capacity. Here we will illustrate a detailed protocol to assess self-renewal of human melanoma stem cells, growing as melanospheres.
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- 2017
- Full Text
- View/download PDF
4. Supplementary Figure 3 from Soluble Human LAG-3 Molecule Amplifies the In vitro Generation of Type 1 Tumor-Specific Immunity
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Chiara Castelli, Giorgio Parmiani, Frédéric Triebel, Licia Rivoltini, Flavio Arienti, Francesca Rini, Chiara Camisaschi, and Chiara Casati
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Supplementary Figure 3 from Soluble Human LAG-3 Molecule Amplifies the In vitro Generation of Type 1 Tumor-Specific Immunity
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- 2023
5. Supplementary Figure 1 from Soluble Human LAG-3 Molecule Amplifies the In vitro Generation of Type 1 Tumor-Specific Immunity
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Chiara Castelli, Giorgio Parmiani, Frédéric Triebel, Licia Rivoltini, Flavio Arienti, Francesca Rini, Chiara Camisaschi, and Chiara Casati
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Supplementary Figure 1 from Soluble Human LAG-3 Molecule Amplifies the In vitro Generation of Type 1 Tumor-Specific Immunity
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- 2023
6. Data from Soluble Human LAG-3 Molecule Amplifies the In vitro Generation of Type 1 Tumor-Specific Immunity
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Chiara Castelli, Giorgio Parmiani, Frédéric Triebel, Licia Rivoltini, Flavio Arienti, Francesca Rini, Chiara Camisaschi, and Chiara Casati
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The adjuvant activities of the human lymphocyte activation gene-3 (LAG-3) molecule have been evaluated in a human setting by investigating the ability of a soluble recombinant human LAG-3 protein (hLAG-3Ig) to enhance the in vitro induction of viral- and tumor-specific CTLs. We found that soluble human LAG-3 significantly sustained the generation and expansion of influenza matrix protein Melan-A/MART-1 and survivin-specific CD8+ T lymphocytes in peripheral blood mononuclear cells (PBMC) of both cancer patients and healthy donors, showing its ability to boost CD8+ T-cell memory response or to prime naive T cells in vitro. The peptide-specific T cells generated in the presence of hLAG-3Ig were endowed with cytotoxic activity and enhanced release of type 1 cytotoxic T (Tc1) cytokines and were able to recognize tumor cells expressing their nominal antigen. Phenotype and cytokine/chemokines produced by antigen-presenting cells (APC) of PBMCs exposed in vitro for 2 days to peptide and hLAG-3Ig indicate that the LAG-3–mediated adjuvant effect may depend on a direct activation of circulating APCs. Our data revealed the activity of hLAG-3Ig in inducing tumor-associated, antigen-specific CD8+ T-cell responses in a human setting and strongly support the conclusion that this recombinant protein is a potential candidate adjuvant for cancer vaccines. (Cancer Res 2006; 66(8): 4450-60)
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- 2023
7. Supplementary Figure 2 from Soluble Human LAG-3 Molecule Amplifies the In vitro Generation of Type 1 Tumor-Specific Immunity
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Chiara Castelli, Giorgio Parmiani, Frédéric Triebel, Licia Rivoltini, Flavio Arienti, Francesca Rini, Chiara Camisaschi, and Chiara Casati
- Abstract
Supplementary Figure 2 from Soluble Human LAG-3 Molecule Amplifies the In vitro Generation of Type 1 Tumor-Specific Immunity
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- 2023
8. Supplementary Methods and Figure Legends from Soluble Human LAG-3 Molecule Amplifies the In vitro Generation of Type 1 Tumor-Specific Immunity
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Chiara Castelli, Giorgio Parmiani, Frédéric Triebel, Licia Rivoltini, Flavio Arienti, Francesca Rini, Chiara Camisaschi, and Chiara Casati
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Supplementary Methods and Figure Legends from Soluble Human LAG-3 Molecule Amplifies the In vitro Generation of Type 1 Tumor-Specific Immunity
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- 2023
9. Impact of hepatitis C virus clearance by direct-acting antiviral treatment on the incidence of major cardiovascular events: A prospective multicentre study
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Vito Di Marco, Vincenza Calvaruso, Salvatore Petta, Mariarosaria Saturnino, Riccardo Nevola, Pia Clara Pafundi, Ferdinando Carlo Sasso, Carmine Coppola, Graziano Troina, Aldo Marrone, Francesca Rini, Laura Staiano, Anna Ludovica Fracanzani, Barbara Guerrera, Mauro Giordano, Luigi Elio Adinolfi, Vincenzo Narciso, Rosa Lombardi, Luca Rinaldi, Antonio Craxì, Antonio Solano, Adinolfi L.E., Petta S., Fracanzani A.L., Coppola C., Narciso V., Nevola R., Rinaldi L., Calvaruso V., Staiano L., Di Marco V., Marrone A., Pafundi P.C., Solano A., Lombardi R., Sasso F.C., Saturnino M., Rini F., Guerrera B., Troina G., Giordano M., Craxi A., Adinolfi, Luigi Elio, Petta, Salvatore, Ludovica Fracanzani, Anna, Coppola, Carmine, Narciso, Vincenzo, Nevola, Riccardo, Rinaldi, Luca, Calvaruso, Vincenza, Staiano, Laura, Di Marco, Vito, Marrone, Aldo, Clara Pafundi, Pia, Solano, Antonio, Lombardi, Rosa, Sasso, Ferdinando Carlo, Saturnino, Mariarosaria, Rini, Francesca, Guerrera, Barbara, Troina, Graziano, Giordano, Mauro, and Craxì, Antonio
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Liver Cirrhosis ,Male ,0301 basic medicine ,Cirrhosis ,Myocardial Ischemia ,Comorbidity ,Hepacivirus ,Disease ,030204 cardiovascular system & hematology ,Chronic hepatitis C ,medicine.disease_cause ,chemistry.chemical_compound ,0302 clinical medicine ,Risk Factors ,Prospective Studies ,Ischemic heart disease, Ischemic cerebral stroke, Chronic hepatitis C, Cirrhosis ,Incidence ,Incidence (epidemiology) ,Smoking ,Middle Aged ,Viral Load ,Stroke ,Italy ,Hypertension ,Female ,Cardiology and Cardiovascular Medicine ,Direct acting ,medicine.medical_specialty ,Ischemic heart disease ,Hepatitis C virus ,Hypercholesterolemia ,Antiviral Agents ,03 medical and health sciences ,Diabetes mellitus ,Internal medicine ,Diabetes Mellitus ,medicine ,Humans ,Viremia ,Aged ,Cirrhosi ,business.industry ,Cholesterol ,Hepatitis C, Chronic ,medicine.disease ,030104 developmental biology ,chemistry ,Relative risk ,Ischemic cerebral stroke ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,business - Abstract
Background and aims: HCV is associated with an increased risk of cardiovascular events (CV). Whether HCV clearance by direct-acting antivirals (DAA) reduces incident CV disease is poorly understood. We investigate whether HCV eradication reduces CV events. Methods: In a prospective multicentre study, 2204 HCV patients (F0–F2:29.5%, F3–F4: 70.5%) were enrolled. Males were 48%, median age was 68 (59–74) years and BMI 25.9 (23.1–28); 24.7% were smokers, 18% had diabetes, 13.2% had cholesterol levels >200 mg/dl and 9.1% took statins, 44% had hypertension. During an overall median follow-up of 28 (24–39) months, incident CV events, such as ischemic heart disease (IHD) and ischemic cerebral stroke (ICS), were recorded. An overall of 2204 patients were evaluated as control group and 1668 patients after HCV elimination were followed as a case group. Factors associated with CV events were evaluated by uni- and multi-variate analyses. Results: Incident CV rates per 100 patient years in pre-treatment and untreated controls and treated cases were 1.12, 1.14 and 0.44 (p = 0.0001 vs. controls), respectively, and a decreased of relative risk (RR = 0.379; p = 0.0002) was observed. CV risk was 2.0–3.5 times lower then in controls (HR 3.671; 95%C.I.:1.871–7.201; p < 0.001). The calculated number of patients to be treated to get a benefit in a patient was 55.26. The annual incidence reduction of CV events was 0.68%. HCV clearance was independently associated with CV events reduction (OR, 4.716; 95% C.I.:1.832–12.138; p = 0.001). Conclusions: HCV clearance by DAA reduces CV events (IHD and ICS) with both clinical and socio-economic benefits.
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- 2020
10. Point‐of‐care HCV RNA testing in the setting of DAA therapy: HCV‐FiS (HEpatitis C Virus Fingerstick Study)
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Vito Di Marco, Elisabetta Conte, Antonio Craxì, Salvatore Petta, Vincenza Calvaruso, Giada Reina, Donatella Ferraro, Francesca Rini, Bianca Magro, Fabrizio Bronte, Calvaruso V., Bronte F., Ferraro D., Reina G., Conte E., Rini F., Magro B., Petta S., Di Marco V., and Craxi A.
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Male ,medicine.medical_specialty ,End of therapy ,Fingerstick ,Hepatitis C virus ,Hepacivirus ,medicine.disease_cause ,Antiviral Agents ,Internal medicine ,TaqMan ,medicine ,Outpatient setting ,Humans ,HCV, DAA ,Aged ,Point of care ,Hepatology ,business.industry ,Venous blood sample ,Middle Aged ,Viral Load ,Hepatitis C ,Point-of-Care Testing ,RNA, Viral ,Female ,business ,Viral load - Abstract
HCV-RNA assessment during therapy with Direct-Acting Antiviral (DAA) regimens still relies on assays requiring blood collection and transport to a specialised laboratory, which may compromise linkage to care. GeneXpert-HCV Viral Load (GXHVL) (Cepheid) is a plasma-based assay used at point of care (POC) with a sensitivity of ≤10IU/mL, and, results available within 2hours. Fifty-nine consecutive HCV-patients ready for DAAs treatment were enrolled. HCV-RNA was simultaneously tested using Roche TaqMan RT-PCR (venous blood sample) and GXHVL (capillary blood collected by fingerstick), at baseline (BL), week 4 (W4) of therapy, end of therapy (EOT) and week 12 of follow-up (W12FU). Both assays demonstrated undetectable HCV-RNA in all patients at EOT and identified the single case of HCV-relapse at W12FU. GXHVL used as a point-of-care assay in the outpatient setting provides results fully comparable to the laboratory-based test. Its excellent performance and ease of use suggest its adoption in non-specialist settings where simplicity of care is paramount to implement HCV eradication campaigns.
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- 2019
11. 1537P Dissecting inflammation in patients with desmoid fibromatosis to identify prognostic biomarkers
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Licia Rivoltini, V. Vallacchi, Alessandro Gronchi, L. Bergamaschi, Federica Perrone, Francesca Rini, Chiara Castelli, and Chiara Colombo
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Pathology ,medicine.medical_specialty ,Oncology ,business.industry ,Desmoid fibromatosis ,medicine ,Inflammation ,In patient ,Hematology ,medicine.symptom ,business - Published
- 2021
12. Author response for 'Reduced incidence of type 2 diabetes in patients with chronic hepatitis C virus infection cleared by direct‐acting antivirals therapy. A prospective study'
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Ferdinando Carlo Sasso, Salvatore Petta, Antonio Solano, Vito Di Marco, Luigi Elio Adinolfi, Luca Rinaldi, Aldo Marrone, Riccardo Nevola, Graziano Troina, Mauro Giordano, Anna Ludovica Fracanzani, Antonio Craxì, Mariarosaria Saturnino, Pia Clara Pafundi, Francesca Rini, Laura Staiano, Carmine Coppola, Barbara Guerrera, Vincenza Calvaruso, Rosa Lombardi, and Vincenzo Narciso
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medicine.medical_specialty ,business.industry ,Incidence (epidemiology) ,Type 2 diabetes ,DIRECT ACTING ANTIVIRALS ,medicine.disease ,Virus ,Chronic hepatitis ,Internal medicine ,Medicine ,In patient ,business ,Prospective cohort study ,Clearance - Published
- 2020
13. Reduced incidence of type 2 diabetes in patients with chronic hepatitis C virus infection cleared by direct-acting antiviral therapy: A prospective study
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Antonio Solano, Anna Ludovica Fracanzani, Ferdinando Carlo Sasso, Salvatore Petta, Pia Clara Pafundi, Antonio Craxì, Riccardo Nevola, Barbara Guerrera, Carmine Coppola, Vito Di Marco, Rosa Lombardi, Vincenzo Narciso, Aldo Marrone, Vincenza Calvaruso, Luigi Elio Adinolfi, Luca Rinaldi, Mariarosaria Saturnino, Mauro Giordano, Francesca Rini, Laura Staiano, Graziano Troina, Adinolfi L.E., Petta S., Fracanzani A.L., Nevola R., Coppola C., Narciso V., Rinaldi L., Calvaruso V., Pafundi P.C., Lombardi R., Staiano L., Di Marco V., Solano A., Marrone A., Saturnino M., Rini F., Guerrera B., Troina G., Giordano M., Craxi A., Sasso F.C., Adinolfi, Luigi E, Petta, Salvatore, Fracanzani, Anna L, Nevola, Riccardo, Coppola, Carmine, Narciso, Vincenzo, Rinaldi, Luca, Calvaruso, Vincenza, Pafundi, Pia Clara, Lombardi, Rosa, Staiano, Laura, Di Marco, Vito, Solano, Antonio, Marrone, Aldo, Saturnino, Mariarosaria, Rini, Francesca, Guerrera, Barbara, Troina, Graziano, Giordano, Mauro, Craxì, Antonio, and Sasso, Ferdinando C
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medicine.medical_specialty ,Cirrhosis ,endocrine system diseases ,Endocrinology, Diabetes and Metabolism ,030209 endocrinology & metabolism ,Type 2 diabetes ,030204 cardiovascular system & hematology ,Antiviral Agents ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,chronic hepatiti ,Internal medicine ,Internal Medicine ,medicine ,Humans ,Glucose homeostasis ,Prospective Studies ,Prospective cohort study ,direct-acting antiviral ,business.industry ,Incidence ,Incidence (epidemiology) ,nutritional and metabolic diseases ,Type 2 Diabetes Mellitus ,Hepatitis C, Chronic ,medicine.disease ,Diabetes Mellitus, Type 2 ,Case-Control Studies ,Relative risk ,HCV ,Population study ,type 2 diabetes ,business ,cirrhosi - Abstract
Aim HCV infection increases the risk of type 2 diabetes mellitus (T2DM). However, it remains still unclear whether HCV clearance by direct-acting antivirals (DAA) reduces T2DM. Therefore, the effect of HCV eradication on T2DM incidence was assessed. Methods A prospective multicenter case-control study was performed, which included 2,426 HCV patients, 42% of which with liver fibrosis F0-F2 and 58% F3-F4. Study population consisted of a control group including 1099 untreated patients and 1327 cases treated with DAA. T2DM incidence was assessed during a follow-up median period of 30 [IQR: 28-42] months. Risk factors of T2DM were assessed by Cox regression model (Relative risk (RR), Hazard risk (HR), Kaplan-Meier). Insulin sensitivity was evaluated by HOMA and changes by ANOVA for repeated measurements. Factors independently associated with T2DM were assessed by multivariate analysis RESULTS: The absolute incidence of T2DM/1,000 person-years for controls and cases was 28 and 7, respectively (p=0.001). In cases compared to controls, HCV clearance reduced the RR and HR of T2DM by 81% and 75-93% respectively (p = 0.001). It has been calculated that for every 15 patients who obtained HCV clearance one case of T2DM is saved. HCV clearance was associated with a significant reduction in HOMA-IR and HOMA- β and an increase in HOMA-S as assessed in 384 patients before and after HCV clearance. At multivariate analysis, HCV clearance emerged as independently associated with a reduced T2DM risk. Conclusion HCV clearance by DAA treatment reduces T2DM incidence more likely by restoring the HCV-induced alteration of glucose homeostasis mechanisms. This article is protected by copyright. All rights reserved.
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- 2020
14. Hepatitis C virus eradication by direct antiviral agents abates oxidative stress in patients with advanced liver fibrosis
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Salvatore Petta, Rosaria Maria Pipitone, Francesca Rini, Alfio Distefano, Agnieszka Micek, Giovanni Li Volti, Stefania Grimaudo, Carlo Castruccio Castracani, Federico Salomone, Michelino Di Rosa, Concetta Gardi, Vito Di Marco, Antonio Craxì, Vincenza Calvaruso, Salomone F., Petta S., Micek A., Pipitone R.M., Distefano A., Castruccio Castracani C., Rini F., Di Rosa M., Gardi C., Calvaruso V., Di Marco V., Li Volti G., Grimaudo S., and Craxi A.
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Liver Cirrhosis ,Male ,medicine.medical_specialty ,Cirrhosis ,Hepatitis C virus ,isoprostanes ,Hepacivirus ,medicine.disease_cause ,Antiviral Agents ,Carotid Intima-Media Thickness ,Gastroenterology ,03 medical and health sciences ,Liver disease ,0302 clinical medicine ,atherosclerosi ,Fibrosis ,Settore BIO/13 - Biologia Applicata ,Internal medicine ,medicine ,Humans ,intima-media thickness ,Aged ,Retrospective Studies ,Settore MED/12 - Gastroenterologia ,Hepatology ,business.industry ,cirrhosis ,Carotid ultrasonography ,lipid peroxidation ,Middle Aged ,medicine.disease ,Hepatitis C ,Isoprostanes ,atherosclerosis ,F ,2 ,Oxidative Stress ,Intima-media thickness ,030220 oncology & carcinogenesis ,030211 gastroenterology & hepatology ,business ,Oxidative stress ,cirrhosi - Abstract
Background and aims: HCV eradication improves non-hepatic outcomes such as cardiovascular diseases, although without clearly defined mechanisms. In this study we aimed to assess whether improvement of carotid atherosclerosis may be linked to a reduction in systemic oxidative stress after viral clearance. Methods: We studied a retrospective cohort of 105 patients (age 62.4±11.2years; 62 men) with F3/F4 fibrosis, characterized by carotid ultrasonography at baseline and at sustained virologic response (SVR) follow-up. Levels of 8-iso-prostaglandin F2α (F2-isoprostanes) and other oxidative stress markers were measured on frozen sera. Association between change (denoted as Δ) in oxidative stress markers (exposures) and change in carotid intima-media thickness (cIMT) (outcome) was examined using multiple linear regression. Results: Subclinical atherosclerosis, defined as the presence of carotid plaque and/or cIMT≥0.9, was present in 72% of the cohort. All patients achieved SVR that led to reduction in cIMT (0.92±0.20 vs 0.83±0.21mm, P 
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- 2020
15. Immune landscape and in vivo immunogenicity of NY-ESO-1 tumor antigen in advanced neuroblastoma patients
- Author
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Francesca Rini, M. Podda, Rosalin Dolores Spagnuolo, Licia Rivoltini, Chiara Camisaschi, Salvatore Lorenzo Renne, Alessandra Tuccitto, Paola Collini, Valeria Beretta, Roberto Luksch, Giorgio Parmiani, and Chiara Castelli
- Subjects
0301 basic medicine ,Cancer Research ,Human leukocyte antigen ,Cancer Vaccines ,lcsh:RC254-282 ,Immune-checkpoints ,03 medical and health sciences ,Neuroblastoma ,0302 clinical medicine ,Immune system ,Immunogenicity, Vaccine ,Lymphocytes, Tumor-Infiltrating ,Antigen ,Antigens, Neoplasm ,T-Lymphocyte Subsets ,Genetics ,Medicine ,Cytotoxic T cell ,Humans ,NY-ESO-1 ,business.industry ,Immunogenicity ,ELISPOT ,Vaccination ,Immunotherapy, Active ,Membrane Proteins ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Tumor antigen ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Child, Preschool ,Immune-contexture ,Cancer research ,Female ,business ,Research Article - Abstract
Background Indirect evidence suggesting the immunosensitivity/immunogenicity of neuroblastoma is accumulating. The aims of this study were to investigate the immune landscape of neuroblastoma and to evaluate the in vivo immunogenicity of the NY-ESO-1 tumor antigen in advanced neuroblastoma patients. Methods The immune infiltrating cells of the NY-ESO-1+ tumors from three HLA*A201 patients with metastatic neuroblastoma who relapsed after conventional treatments were evaluated by immunohistochemistry. The patients were vaccinated with the HLA-A*0201-restricted peptide NY-ESO-1157-165(V). The peptide was emulsified in Montanide ISA51 and given subcutaneously in a phase I pilot study. The immunogenicity of NY-ESO-1 antigen was evaluated by monitoring mononuclear cells in patient peripheral blood, pre- and post-vaccine, by short-term in vitro sensitization, HLA-multimer staining and IFN-γ ELISpot analysis. Results Both CD3 T cells and CD163 myeloid cells were present in pre-vaccine tumors and PD-1 and PD-L1 expression was mainly found in the immune infiltrate. Despite the advanced stage of the disease, the vaccination induced systemic NY-ESO-1 specific CD8 T cells releasing IFN-γ in response to activation with the NY-ESO-1 peptide and an HLA-A2 positive neuroblastoma cell line. Conclusions Our results indicate that vaccination with a tumor-associated peptide is able to boost NY-ESO-1-specific, functionally active T cells in advanced neuroblastoma patients with lymphocyte infiltration in their pre-vaccine tumors. Trial registration EudraCT #2006–002859-33. Electronic supplementary material The online version of this article (10.1186/s12885-018-4910-8) contains supplementary material, which is available to authorized users.
- Published
- 2018
16. 1 Dissecting β-catenin associated inflammation in patients with desmoid fibromatosis to identify prognostic biomarkers
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Laura Bergamaschi, Viviana Vallacchi, Chiara Castelli, Chiara Colombo, Licia Rivoltini, Federica Perrone, Alessandro Gronchi, and Francesca Rini
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Pharmacology ,Cancer Research ,business.industry ,Immunology ,Desmoid fibromatosis ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Inflammation ,Oncology ,Catenin ,medicine ,Cancer research ,Molecular Medicine ,Immunology and Allergy ,In patient ,medicine.symptom ,business ,RC254-282 - Abstract
BackgroundDesmoid fibromatosis (DF) is a locally aggressive rare tumor with high recurrence rate after surgery and unpredictable clinical course. Standard of care for DF patients is active surveillance; however, 30% of patients will progress and need active treatments. Biomarkers discriminating aggressive forms of DF are not available and prediction of progressing patients remains challenging. DF harbors mutations in β-catenin and a transcriptional ‘inflammatory phenotype’. Cancer-associated inflammation is fostered by systemic factors and detectable in circulating immune cells. Blood leukocytes thus represent a promising source of prognostic biomarkers for DF patients. In this study we investigate phenotypic and functional features of peripheral blood immune cells and molecular profile of DF biopsies to identify DF patients at risk of progression and guide tailored therapeutic approaches.MethodsThis is a prospective observational study enrolling patients with primary sporadic desmoid fibromatosis under active surveillance (n=80). Tumor and blood samples collected at diagnosis and during active surveillance will be studied by 1. transcriptomic analysis of DF biopsies; 2. multiparametric flowcytometry and functional profiling of blood cells; 3. RNA profiling of whole blood; 4. evaluation of plasma levels of cyto/chemokine and ctDNA of β-catenin variants. Levels of blood analytes will be correlated with patients‘ clinical outcome and integrated with immunological parameters.ResultsPeripheral blood immune profile of 42 cases and 17 healthy donors (HD) shows that DF patients display at baseline an altered myeloid profile compared to HD, which is maintained in a subset of patients during the first year of active surveillance. An increase in immunosuppressive activated granulocytes and granulocytic myeloid-derived suppressor cells, defined by differential co-expression of CD15, CD11b, CD16 and LOX1, is observed, concomitantly, with a boost of monocyte subsets, defined by co-expression of CD33, CD11b, CD14, CD16, HLA-DR and PDL1. Immunosuppressive low density granulocytes are increased in progressing patients compared to HD and regressors. Of note, a significant up-regulation of immunosuppressive PMN-MDSC (defined as CD15+LOX-1+) is observed in DF harboring T41A mutation, but not in S45 mutated DF.Transcriptomic data of DF biopsies and of plasma analytes are ongoing.ConclusionsSystemic alterations of immunosuppressive and inflammatory myeloid cell subsets in peripheral blood of DF patients indicate that the inflammatory status detected at tumor site is reflected at systemic level. The altered myeloid profile supports the involvement of the immune system in DF onset and may represent a marker of disease aggressiveness.AcknowledgementsSupported by Italian Ministry of Health (RF-2016-02362609).Trial RegistrationNot applicable.ReferencesNot applicable.Ethics ApprovalThe study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Ethics Committee of Fondazione IRCCS Istituto Nazionale dei Tumori di Milano (protocol code INT85/10).ConsentWritten informed consent was obtained from the patient for publication of this abstract. A copy of the written consent is available for review by the Editor of this journal.
- Published
- 2021
17. Direct-acting antivirals after successful treatment of early hepatocellular carcinoma improve survival in HCV-cirrhotic patients
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A. Averna, Rete Sicilia Selezione Terapia – Hcv, Giovanni Raimondo, F. Cartabellotta, Salvatore Guastella, Giuseppe Alaimo, Vito Di Marco, Bianca Magro, Giovanni Mazzola, L. Larocca, M.R. Cannavò, Anna Licata, Gaetano Bertino, Salvatore Madonia, Irene Cacciola, Marco Distefano, Giuseppe Cabibbo, G. Scifo, N. Alessi, Giovanni Squadrito, Antonio Craxì, Franco Trevisani, Salvatore Petta, Margherita Rossi, Maurizio Russello, Francesca Rini, Calogero Cammà, Maria Antonietta Di Rosolini, Ciro Celsa, Giuseppe Malizia, Tullio Prestileo, Vincenza Calvaruso, I. Scalisi, F. Benanti, Cabibbo G., Celsa C., Calvaruso V., Petta S., Cacciola I., Cannavo M.R., Madonia S., Rossi M., Magro B., Rini F., Distefano M., Larocca L., Prestileo T., Malizia G., Bertino G., Benanti F., Licata A., Scalisi I., Mazzola G., Di Rosolini M.A., Alaimo G., Averna A., Cartabellotta F., Alessi N., Guastella S., Russello M., Scifo G., Squadrito G., Raimondo G., Trevisani F., Craxi A., Di Marco V., Camma C., and Cammà Calogero.
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Male ,0301 basic medicine ,medicine.medical_specialty ,Survival rate ,Carcinoma, Hepatocellular ,Cirrhosis ,Sustained Virologic Response ,Prognosi ,Hepatitis C virus (HCV), Hepatocellular carcinoma (HCC), Direct-acting antiviral (DAA), Overall survival, Prognosis, Survival rate, Liver cirrhosis ,Hepacivirus ,Antiviral Agents ,Gastroenterology ,Liver cirrhosi ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Early Hepatocellular Carcinoma ,Overall survival ,Prospective Studies ,Hepatocellular carcinoma (HCC) ,Propensity Score ,Aged ,Aged, 80 and over ,Hepatology ,business.industry ,Liver Neoplasms ,Hazard ratio ,Direct-acting antiviral (DAA) ,Hepatitis C ,Hepatitis C virus (HCV) ,Middle Aged ,medicine.disease ,Prognosis ,Liver cirrhosis ,030104 developmental biology ,Hepatocellular carcinoma ,Female ,030211 gastroenterology & hepatology ,Neoplasm Recurrence, Local ,Liver cancer ,business ,Viral hepatitis ,Follow-Up Studies - Abstract
Background & Aims: The effectiveness of direct-acting antivirals (DAAs) against hepatitis C virus (HCV), following successful treatment of early hepatocellular carcinoma (HCC), has been studied extensively. However, the benefit in terms of overall survival (OS) remains to be conclusively demonstrated. The aim of this study was to assess the impact of DAAs on OS, HCC recurrence, and hepatic decompensation. Methods: We prospectively enrolled 163 consecutive patients with HCV-related cirrhosis and a first diagnosis of early Barcelona Clinic Liver Cancer stage 0/A HCC, who had achieved a complete radiologic response after curative resection or ablation and were subsequently treated with DAAs. DAA-untreated patients from the ITA.LI.CA. cohort (n = 328) served as controls. After propensity score matching, outcomes of 102 DAA-treated (DAA group) and 102 DAA-untreated patients (No DAA group) were compared. Results: In the DAA group, 7/102 patients (6.9%) died, HCC recurred in 28/102 patients (27.5%) and hepatic decompensation occurred in 6/102 patients (5.9%), after a mean follow-up of 21.4 months. OS was significantly higher in the DAA group compared to the No DAA group (hazard ratio [HR] 0.39; 95% CI 0.17–0.91; p = 0.03). HCC recurrence was not significantly different between the DAA and No DAA groups (HR 0.70; 95% CI 0.44–1.13; p = 0.15). A significant reduction in the rate of hepatic decompensation was observed in the DAA group compared with the No DAA group (HR 0.32; 95% CI 0.13–0.84; p = 0.02). In the DAA group, sustained virologic response was a significant predictor of OS (HR 0.02; 95% CI 0.00–0.19; p
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- 2019
18. Aminopyrine breath test predicts liver-related events and death in HCV-related cirrhosis on SVR after DAA therapy
- Author
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Calogero Cammà, Vito Di Marco, Francesca Rini, S. Ciminnisi, Vincenza Calvaruso, Rosaria Maria Pipitone, Salvatore Petta, Antonio Craxì, Edoardo G. Giannini, Stefania Grimaudo, Petta S., Rini F., Calvaruso V., Camma C., Ciminnisi S., Di Marco V., Giannini E.G., Grimaudo S., Maria Pipitone R., and Craxi A.
- Subjects
Liver Cirrhosis ,medicine.medical_specialty ,Cirrhosis ,Sofosbuvir ,Hepatitis C virus ,Hepacivirus ,medicine.disease_cause ,Antiviral Agents ,Gastroenterology ,Internal medicine ,Humans ,Medicine ,Decompensation ,Aminopyrine ,Child ,CIRRHOSIS ,Hepatic encephalopathy ,aminopyrine breath test ,Breath test ,Hepatology ,medicine.diagnostic_test ,direct antiviral agent ,Cumulative dose ,business.industry ,Hepatitis C, Chronic ,medicine.disease ,Hepatitis C ,Breath Tests ,liver function ,Liver function ,business ,DIRECT ANTIVIRAL AGENTS ,AMINOPYRINE BREATH TEST ,LIVER FUNCTION ,medicine.drug ,cirrhosi - Abstract
Background & Aims: In patients with hepatitis C virus (HCV)-related advanced cirrhosis, the effects of sustained virological response (SVR) by direct antiviral agents (DAAs) on decompensation and liver deaths are less clearcut, since up to 30% of patients do not improve, and no predictors of outcome have been identified. We used 13C-aminopyrine breath test (ABT) to assess whether its changes can predict liver-related outcomes after DAA treatment in patients with HCV cirrhosis. Methods: Fifty consecutive patients with HCV cirrhosis were enrolled. Patients were included if they had Child A cirrhosis at risk for decompensation – defined as Child A6 (N=22, 44%) or previous decompensation (N=7, 14%) – or Child B cirrhosis (N=21, 42%) eligible for DAA-based antiviral therapy. ABT was performed at baseline and 12weeks after the end of antiviral therapy. Patients received sofosbuvir-based regimens. Results: Aminopyrine breath test was available for all 50 patients at baseline. The 120’ cumulative dose was directly associated at regression analysis only with albumin levels (P=.001). ABT was available at follow-up week 12 for 41 patients (FUW12), all with SVR, and followed for a median of 25.2months (range 12.2-32.1months). Lower Ʌ ABT – defined as changes of 120’ cumulative dose from FUW12 to baseline – (HR 0.97, 95% CI 0.94-0.99; P=.02) and FUW12 hepatic encephalopathy (HR 19.0, 95% CI 1.16-310.3; P=.03) were the only independent predictors of liver events/death at multivariate Cox regression analysis. The AUC of Ʌ ABT was good (0.87, 95% CI 0.75-0.97), with a delta ≥0% well discriminating patients at lower vs patients at higher risk of liver-related events/death (P 
- Published
- 2019
19. Hepatobiliary phase in cirrhotic patients with different Model for End-stage Liver Disease score: comparison of the performance of gadoxetic acid to gadobenate dimeglumine
- Author
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Claudia Khouri Chalouhi, Federica Vernuccio, Angelo Vanzulli, Francesca Rini, Bruno Tuscano, Piergiorgio Duca, Giuseppe Brancatelli, Khouri Chalouhi C., Vernuccio F., Rini F., Duca P., Tuscano B., Brancatelli G., and Vanzulli A.
- Subjects
Liver Cirrhosis ,Adult ,Male ,Gadolinium DTPA ,Gadoxetic acid ,medicine.medical_specialty ,Liver Cirrhosi ,Contrast Media ,Sensitivity and Specificity ,Severity of Illness Index ,030218 nuclear medicine & medical imaging ,Gadobenic acid ,03 medical and health sciences ,Liver disease ,Young Adult ,0302 clinical medicine ,Model for End-Stage Liver Disease ,Meglumine ,Retrospective Studie ,medicine ,Gadolinium ethoxybenzyl DTPA ,Organometallic Compounds ,Humans ,Radiology, Nuclear Medicine and imaging ,Retrospective Studies ,Neuroradiology ,Aged ,Aged, 80 and over ,Cross-Sectional Studie ,medicine.diagnostic_test ,business.industry ,Magnetic resonance imaging ,General Medicine ,Odds ratio ,Middle Aged ,medicine.disease ,Magnetic Resonance Imaging ,Cross-Sectional Studies ,030220 oncology & carcinogenesis ,Female ,Radiology ,Nuclear medicine ,business ,medicine.drug ,Human - Abstract
The purpose of this study was to compare the performance of gadobenate dimeglumine–enhanced MRI and gadoxetic acid–enhanced MRI in the hepatobiliary phase (HBP) in cirrhotic patients with different degrees of liver dysfunction. In this retrospective cross-sectional study, we analyzed the unenhanced phase and the HBP of 131 gadobenate dimeglumine–enhanced MRI examinations (gadobenate dimeglumine group) and 127 gadoxetic acid–enhanced MRI examinations (gadoxetic acid group) performed in 249 cirrhotic patients (181 men and 68 women; mean age, 64.8 years) from August 2011 to April 2017. For each MRI, the contrast enhancement index of the liver parenchyma was calculated and correlated to the Model For End-Stage Liver Disease (MELD) score (multiple linear regression analysis). A qualitative analysis of the adequacy of the HBP, adjusted for the MELD score (logistic regression analysis), was performed. The contrast enhancement index was inversely related (r = − 0.013) with MELD score in both gadoxetic acid and gadobenate dimeglumine group. At the same MELD score, the contrast enhancement index in the gadoxetic acid group was increased by a factor of 0.23 compared to the gadobenate dimeglumine group (p 10, if the hepatobiliary phase is clinically indicated. • In patients with high MELD score (> 15), the administration of the hepatobiliary agent could be useless; even though, if it is clinically indicated, we recommend to use gadoxetic acid given the higher probability of obtaining clinically relevant information.
- Published
- 2019
20. Immunomodulatory Factors Control the Fate of Melanoma Tumor Initiating Cells
- Author
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Mario Santinami, Angela Greco, Licia Rivoltini, Valeria Beretta, Alessandra Tuccitto, Giacomo Manenti, Roberto Patuzzo, Marcella Tazzari, Malcolm R. Alison, Claudia Miranda, Barbara Vergani, Michela Perego, Chiara Castelli, Loredana Cleris, Daniele Giardiello, Antonello Villa, Francesca Rini, Tuccitto, A, Tazzari, M, Beretta, V, Rini, F, Miranda, C, Greco, A, Santinami, M, Patuzzo, R, Vergani, B, Villa, A, Manenti, G, Cleris, L, Giardiello, D, Alison, M, Rivoltini, L, Castelli, C, and Perego, M
- Subjects
0301 basic medicine ,congenital, hereditary, and neonatal diseases and abnormalities ,Microenvironment ,Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2] ,Cellular differentiation ,Context (language use) ,Biology ,tumor-initiating cells ,Tumor-initiating cell ,03 medical and health sciences ,Paracrine signalling ,Neutralization Tests ,Cell Line, Tumor ,Spheroids, Cellular ,Paracrine Communication ,mental disorders ,cytokine ,medicine ,Humans ,Immunologic Factors ,Cell Lineage ,Cell Self Renewal ,Autocrine signalling ,Melanoma ,Cellular Senescence ,Tumor microenvironment ,Interleukin-6 ,Cell Differentiation ,Cell Biology ,medicine.disease ,Xenograft Model Antitumor Assays ,Interleukin-10 ,Immune surveillance ,Autocrine Communication ,Interleukin 10 ,Phenotype ,030104 developmental biology ,Immunology ,Neoplastic Stem Cells ,Cancer research ,Molecular Medicine ,Receptors, Chemokine ,Stem cell ,human activities ,Developmental Biology - Abstract
Melanoma is a highly heterogeneous tumor for which recent evidence supports a model of dynamic stemness. Melanoma cells might temporally acquire tumor-initiating properties or switch from a status of tumor-initiating cells (TICs) to a more differentiated one depending on the tumor context. However, factors driving these functional changes are still unknown. We focused on the role of cyto/chemokines in shaping TICs isolated directly from tumor specimens of two melanoma patients, namely Me14346S and Me15888S. We analyzed the secretion profile of TICs and of their corresponding melanoma differentiated cells and we tested the ability of cyto/chemokines to influence TIC self-renewal and differentiation. We found that TICs, grown in vitro as melanospheres, had a complex secretory profile as compared to their differentiated counterparts. Some factors, such as CCL-2 and IL-8, also produced by adherent melanoma cells and melanocytes did not influence TIC properties. Conversely, IL-6, released by differentiated cells, reduced TIC self-renewal and induced TIC differentiation while IL-10, produced by Me15888S, strongly promoted TIC self-renewal through paracrine/autocrine actions. Complete neutralization of IL-10 activity by gene silencing and antibody-mediated blocking of the IL-10Rα was required to sensitize Me15888S to IL-6-induced differentiation. For the first time these results show that functional heterogeneity of melanoma could be directly influenced by inflammatory and suppressive soluble factors, with IL-6 favoring TIC differentiation, and IL-10 supporting TIC self-renewal. Thus, understanding the tumor microenvironment (TME) role in modulating melanoma TIC phenotype is fundamental to identifying novel therapeutic targets to achieve long-lasting regression of metastatic melanoma.
- Published
- 2016
21. Hepatitis C Virus Eradication by Direct Antiviral Agents Improves Carotid Atherosclerosis in patients with Severe Liver Fibrosis
- Author
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Anna Ludovica Fracanzani, Riccardo Nevola, Anna Licata, Marcello Ciaccio, Silvia Fargion, Rosaria Maria Pipitone, Rosalia Caldarella, Antonio Pinto, Luigi Elio Adinolfi, Antonino Tuttolomondo, Vincenza Calvaruso, Luca Rinaldi, Vito Di Marco, Stefania Grimaudo, Luca Valenti, Salvatore Petta, Calogero Cammà, Aldo Marrone, Antonio Craxì, Francesca Rini, Daniele Torres, Petta, S, Adinolfi, Le, Fracanzani, Al, Rini, F, Caldarella, R, Calvaruso, V, Cammà, C, Ciaccio, M, Di Marco, V, Grimaudo, S, Licata, A, Marrone, A, Nevola, R, Pipitone, Rm, Pinto, A, Rinaldi, L, Torres, D, Tuttolomondo, A, Valenti, L, Fargion, S, Craxì, A., Petta, Salvatore, Adinolfi, Luigi Elio, Fracanzani, Anna Ludovica, Rini, Francesca, Caldarella, Rosalia, Calvaruso, Vincenza, Cammà, Calogero, Ciaccio, Marcello, Di Marco, Vito, Grimaudo, Stefania, Licata, Anna, Marrone, Aldo, Nevola, Riccardo, Pipitone, Rosaria Maria, Pinto, Antonio, Rinaldi, Luca, Torres, Daniele, Tuttolomondo, Antonino, Valenti, Luca, Fargion, Silvia, and Craxì, Antonio
- Subjects
0301 basic medicine ,Carotid atherosclerosis ,Carotid Artery Diseases ,Male ,medicine.medical_specialty ,Cirrhosis ,SVR ,Sustained Virologic Response ,Hepatitis C virus ,Hepacivirus ,medicine.disease_cause ,Gastroenterology ,Antiviral Agents ,Carotid Intima-Media Thickness ,03 medical and health sciences ,Liver disease ,0302 clinical medicine ,Risk Factors ,Internal medicine ,Diabetes mellitus ,medicine ,Glucose homeostasis ,Humans ,In patient ,Prospective Studies ,DAA ,Hepatology ,business.industry ,Hepatitis C, Chronic ,Middle Aged ,medicine.disease ,030104 developmental biology ,Treatment Outcome ,ATHEROSCLEROSIS ,HCV ,cardiovascular system ,030211 gastroenterology & hepatology ,Female ,business ,Direct acting ,Follow-Up Studies - Abstract
BACKGROUND AND AIM: Recent studies suggest an association between HCV infection and cardiovascular damage, including carotid atherosclerosis, with a possible effect of HCV clearance on cardiovascular outcomes. We aimed to examine whether HCV eradication by direct antiviral agents (DAA) improves carotid atherosclerosis in HCV-infected patients with advanced fibrosis/compensated cirrhosis. MATERIALS AND METHODS: One hundred eighty-two consecutive HCV patients with advanced fibrosis or compensated cirrhosis were evaluated by virological, anthropometric and metabolic measurements. All patients underwent DAA-based antiviral therapy according to AISF/EASL guidelines. Intima-media thickness (IMT), carotid thickening (IMT≥1 mm) and carotid plaques, defined as focal thickening of ≥ 1.5 mm at the level of common carotid, were evaluated by ultrasonography (US) at baseline and 9-12 months after the end of therapy. RESULTS: Fifty-six percent of patients were males, mean age was 63.1±10.4 years and 65.9% had compensated cirrhosis. One patient out of five had diabetes, 14.3% were obese, 41.8% had arterial hypertension and 35.2% were smokers. Mean IMT was 0.94±0.29 mm, 42.9% had IMT≥1 mm, and 42.9% had carotid plaques. All patients achieved a 12-weeks sustained virological response. IMT significantly decreased from baseline to follow-up (0.94±0.29 mm vs. 0.81±0.27, p
- Published
- 2018
22. Hepatitis C virus eradication by direct antiviral agents improves carotid atherosclerosis in patients with advanced fibrosis/compensated cirrhosis
- Author
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C. Cammà, Luca Rinaldi, Daniele Torres, A.L. Fracanzani, S. Petta, Antonio Craxì, Vincenza Calvaruso, Le Adinolfi, V. Di Marco, Francesca Rini, Riccardo Nevola, Silvia Fargion, A. Pinto, Aldo Marrone, A. Tuttolomondo, Luca Valenti, Petta, S, Adinolfi, Le, Fracanzani, Al, Calvaruso, V, Rini, F, Camma, C, V Di Marco, Marrone, A, Nevola, R, Pinto, A, Rinaldi, L, Torres, D, Tuttolomondo, A, Valenti, Gian Lorenzo, Fargion, S, and Craxì, A
- Subjects
Carotid atherosclerosis ,medicine.medical_specialty ,Cirrhosis ,Hepatology ,business.industry ,Hepatitis C virus ,Gastroenterology ,medicine.disease ,medicine.disease_cause ,Advanced fibrosis ,Internal medicine ,medicine ,In patient ,business - Published
- 2018
23. Biological quality control for extracorporeal photochemotherapy: Assessing mononuclear cell apoptosis levels in ECP bags of chronic GvHD patients
- Author
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Annalisa Birolini, Flavio Arienti, Arabella Mazzocchi, Francesca Rini, Laura Terranova, Francesca Taverna, Fernando Ravagnani, Cecilia Melani, Paola Coluccia, and Luigi Mariani
- Subjects
medicine.diagnostic_test ,business.industry ,Hematology ,General Medicine ,Lymphocyte proliferation ,medicine.disease ,Peripheral blood mononuclear cell ,Flow cytometry ,Lymphoma ,chemistry.chemical_compound ,chemistry ,Annexin ,Apoptosis ,Immunology ,Extracorporeal photochemotherapy ,Medicine ,Propidium iodide ,business - Abstract
Extracorporeal photochemotherapy (ECP) is a treatment approved by the FDA for cutaneous T-cell lymphoma, and it is currently used off-label for graft-versus-host disease (GvHD) and other conditions. In agreement with good practices for the therapeutic use of human cells, quality control has to be performed to validate the ECP procedure with the off-line technique. Since no gold-standard biological test is available, we assessed the apoptosis generated in the ECP bag using a flow cytometric analysis. Thirty-one ECP procedures performed on 13 patients with chronic GvHD were studied by monitoring the induction of mononuclear cell (MNC) apoptosis using annexin V/propidium iodide double staining; residual lymphocyte proliferation to standard mitogens was also measured in 17 of the procedures. The kinetics of apoptosis was analyzed at different times in MNCs untreated or treated with 8-methoxy-psoralen plus ultraviolet A; the variation (ΔAPOPTOSIS ) after 24 h revealed the efficacy of the treatment. In 88.6% of the 31 ECP procedures, ΔAPOPTOSIS was >15% (the "alerting" threshold for ΔAPOPTOSIS was set at 15% on the basis of our data); in the remainder (19.4%), the increment in apoptosis was lower. In four procedures, the proliferation assay was useful for assessing the effect of ECP on the apheretic bag. In conclusion, both flow cytometric assays enabled a biologically significant result to be obtained. In our opinion, the apoptosis test-being faster and easier than the proliferation test-could be a reliable way to validate ECP procedures.
- Published
- 2014
24. Hepatitis C Virus eradication by direct antiviral agents improves carotid atherosclerosis in patients with advanced fibrosis/compensated cirrhosis
- Author
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Vincenza Calvaruso, C. Cammà, Silvia Fargion, Aldo Marrone, Daniele Torres, Luca Rinaldi, A. Tuttolomondo, A.L. Fracanzani, A. Pinto, Riccardo Nevola, S. Petta, Le Adinolfi, Vito Di Marco, Francesca Rini, Mauro Giordano, Luca Valenti, and Antonio Craxì
- Subjects
Carotid atherosclerosis ,medicine.medical_specialty ,Cirrhosis ,Hepatology ,business.industry ,Hepatitis C virus ,medicine.disease ,medicine.disease_cause ,Gastroenterology ,Advanced fibrosis ,Internal medicine ,medicine ,In patient ,business - Published
- 2018
25. SAT-223-AA genotype of the deSNP rs6726639 of gene MERTK (MER Tyrosine Kinase) is associated with development of hepatocellular carcinoma after hepatitis C virus clearance
- Author
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Vito Di Marco, Lorenza Di Marco, Vincenza Calvaruso, Salvatore Petta, Francesca Rini, Bianca Magro, Elisabetta Conte, Rosaria Maria Pipitone, Antonio Craxì, Calogero Cammà, Stefania Grimaudo, Giuseppe Cabibbo, and Ciro Celsa
- Subjects
Hepatology ,Hepatitis C virus ,Hepatocellular carcinoma ,Genotype ,Cancer research ,medicine ,MERTK ,Biology ,medicine.disease_cause ,medicine.disease ,Gene ,Tyrosine kinase - Published
- 2019
26. OC.07.1 DIRECT ACTING ANTIVIRALS AFTER SUCCESSFUL TREATMENT OF EARLY HEPATOCELLULAR CARCINOMA IMPROVE SURVIVAL AND REDUCE HEPATIC DECOMPENSATION IN HCV-CIRRHOTIC PATIENTS
- Author
-
V. Di Marco, Francesca Rini, Giuseppe Cabibbo, F. Cartabellotta, Giovanni Squadrito, N. Alessi, Marco Distefano, Salvatore Guastella, Tullio Prestileo, Giuseppe Alaimo, Bianca Magro, A. Averna, Antonio Craxì, F. Benanti, G. Raimondo, M.A. Di Rosolini, Vincenza Calvaruso, C. Cammà, A. Licata, I. Scalisi, L. Larocca, Ciro Celsa, S. Petta, M.R. Cannavò, Irene Cacciola, Marcos A. Rossi, G. Scifo, S. Madonia, Giovanni Mazzola, Giuseppe Malizia, Gaetano Bertino, and Maurizio Russello
- Subjects
medicine.medical_specialty ,Hepatology ,business.industry ,Internal medicine ,Gastroenterology ,medicine ,Early Hepatocellular Carcinoma ,business ,DIRECT ACTING ANTIVIRALS ,Hepatic decompensation - Published
- 2019
27. Effects of HCV eradication by DAA on oxidative stress parameters in patients with chronic hepatitis C
- Author
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Fabio Galvano, Vincenza Calvaruso, Rosaria Maria Pipitone, Antonio Craxì, Stefania Grimaudo, C.C. Castracane, Federico Salomone, S. Petta, Alfio Distefano, G. Li Volti, V. Di Marco, and Francesca Rini
- Subjects
medicine.medical_specialty ,Hepatology ,Chronic hepatitis ,business.industry ,Internal medicine ,Gastroenterology ,medicine ,In patient ,medicine.disease_cause ,business ,Oxidative stress - Published
- 2019
28. Changes in 13C-aminopyrine breath test predict liver-related events and death in patients with HCV-related previous decompensated child A5 or child A6 to B cirrhosis who achieve SVR after DAA therapy
- Author
-
Rosaria Maria Pipitone, S. Ciminnisi, S. Petta, V. Di Marco, Francesca Rini, C. Cammà, Stefania Grimaudo, E.G. Giannini, Vincenza Calvaruso, and Antonio Craxì
- Subjects
Breath test ,medicine.medical_specialty ,Cirrhosis ,Hepatology ,medicine.diagnostic_test ,business.industry ,Internal medicine ,Gastroenterology ,medicine ,In patient ,medicine.disease ,business - Published
- 2019
29. AA genotype of deSNP rs6726639 of MERTK gene is associated with development of Hepatocellular Carcinoma after eradication of Hepatitis C Virus infection
- Author
-
Antonio Craxì, Vincenza Calvaruso, M.R. Pipitone, S. Petta, C. Cammà, Giuseppe Cabibbo, Bianca Magro, Ciro Celsa, Stefania Grimaudo, V. Di Marco, Francesca Rini, Elisabetta Conte, and L. Di Marco
- Subjects
MERTK Gene ,Hepatology ,business.industry ,Hepatocellular carcinoma ,Hepatitis C virus ,Genotype ,Gastroenterology ,medicine ,medicine.disease ,medicine.disease_cause ,business ,Virology - Published
- 2019
30. Melan-A/MART-1 immunity in a EWS-ATF1 translocated clear cell sarcoma patient treated with sunitinib: a case report
- Author
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Carlo Morosi, Antonello Villa, Marcella Tazzari, Silvia Stacchiotti, Chiara Castelli, Francesca Rini, Chiara Colombo, Elena Palassini, Silvana Pilotti, Licia Rivoltini, Tiziana Negri, Barbara Vergani, Paolo G. Casali, Flavio Crippa, Tazzari, M, Palassini, E, Vergani, B, Villa, A, Rini, F, Negri, T, Colombo, C, Crippa, F, Morosi, C, Casali, P, Pilotti, S, Stacchiotti, S, Rivoltini, L, and Castelli, C
- Subjects
Adult ,Cancer Research ,Indoles ,Oncogene Proteins, Fusion ,Transcription Factor ,medicine.medical_treatment ,Case Report ,Antineoplastic Agents ,Pyrrole ,Immunophenotyping ,Antineoplastic Agent ,Lymphocytes, Tumor-Infiltrating ,MART-1 Antigen ,Immune system ,Tumor-specific T cell ,Melanocyte differentiation ,Antigens, Neoplasm ,Sunitinib ,Genetics ,medicine ,Chemotherapy ,Humans ,Pyrroles ,Neoplasm Staging ,business.industry ,Melanoma ,Soft tissue sarcoma ,Sarcoma ,Immunotherapy ,medicine.disease ,Treatment Outcome ,Oncology ,Indole ,Positron-Emission Tomography ,Immunology ,Cancer research ,Female ,Sarcoma, Clear Cell ,Clear-cell sarcoma ,Tomography, X-Ray Computed ,business ,Clear cell sarcoma ,Human ,Transcription Factors ,medicine.drug - Abstract
Background: Clear cell sarcoma (CCS), initially named malignant melanoma of soft parts, is an aggressive soft tissue sarcoma (STS) that, due to MITF activation, shares with melanoma the expression of melanocyte differentiation antigens. CCS is poorly sensitive to chemotherapy. Multi-kinase inhibitors have been used as therapeutic agents. In the case we report here, treatment with sunitinib induced a long-lasting clinical response that was associated with an immune activation directed against Melan-A/MART-1 antigen. Case presentation: A 28years old female patient with an advanced molecularly confirmed CCS resistant to conventional chemotherapy was started in January 2012 on sunitinib, 37.5mg/day, with evidence of radiologic and metabolic response at the primary and metastatic sites of disease. Pathologic response and loss of the Melan-A/MART-1 antigen were evidenced on residual tumor removed in April 2012. Immunological monitoring performed on patient's blood during pharmacological treatment revealed a systemic, Melan-A/MART-1 specific immunity and a low frequency of immunosuppressive cells. Sunitinib was restarted in May 2012, with a new response, and continued for 11months although with repeatedly interruptions due to toxicity. Disease progression and new responses were documented at each treatment interruption and restart. Sunitinib was definitively interrupted in April 2013 for disease progression. Conclusion: The analysis of this case proves that antigens expressed by CCS, as for melanoma, can be immunogenic in vivo and that tumor-antigen specific T cells may exert anti-tumor activity in CCS patient. Thus, manipulation of the immune response may have therapeutic potential for this STS subtype and immunotherapy approaches, can be promising therapeutic options for these patients.
- Published
- 2015
31. Adaptive immune contexture at the tumour site and downmodulation of circulating myeloid-derived suppressor cells in the response of solitary fibrous tumour patients to anti-angiogenic therapy
- Author
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Antonello Villa, Licia Rivoltini, Marcella Tazzari, Silvia Stacchiotti, M. Fiore, Francesca Rini, S. Pilotti, Tiziana Negri, Barbara Vergani, Chiara Colombo, Veronica Huber, Alessandro Gronchi, Paolo G. Casali, Paolo G. Dagrada, Chiara Castelli, Tazzari, M, Negri, T, Rini, F, Vergani, B, Huber, V, Villa, A, Dagrada, P, Colombo, C, Fiore, M, Gronchi, A, Stacchiotti, S, Casali, P, Pilotti, S, Rivoltini, L, and Castelli, C
- Subjects
Adult ,Male ,Cancer Research ,Pathology ,medicine.medical_specialty ,Solitary fibrous tumor ,Indoles ,myeloid-derived suppressor ,medicine.medical_treatment ,Angiogenesis Inhibitors ,Biology ,Adaptive Immunity ,Disease-Free Survival ,law.invention ,anti-angiogenic therapy ,Immune system ,law ,medicine ,Sunitinib ,Tumor Microenvironment ,Humans ,anti-tumour response ,Pyrroles ,Lymphocytes ,tumour-infiltrating lymphocytes ,Myeloid Progenitor Cells ,Aged ,Immunosuppression Therapy ,Tumor microenvironment ,immune contexture ,Immunosuppression ,Middle Aged ,medicine.disease ,Acquired immune system ,myeloid-derived suppressor cells ,Tumour site ,Treatment Outcome ,Oncology ,Solitary Fibrous Tumors ,soft tissue sarcoma ,immunohistochemistry ,Myeloid-derived Suppressor Cell ,Suppressor ,solitary fibrous tumour ,Female ,Translational Therapeutics ,tumour microenvironment - Abstract
Background: Host immunity is emerging as a key player in the prognosis and response to treatment of cancer patients. However, the impact of the immune system and its modulation by therapies are unknown in rare soft tissue sarcomas such as solitary fibrous tumours (SFTs), whose management in the advanced forms includes anti-angiogenic therapy. Here, we studied the in situ and systemic immune status of advanced SFT patients and the effects of sunitinib malate (SM) in association with the clinical efficacy. Methods: Immune contexture of SFTs was assessed by immunohistochemistry in lesions from untreated or SM-treated patients. Frequency of circulating myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs) and T-cell functions was assessed ex vivo in SFT patients prior and during anti-angiogenic therapy. Patients with long-term tumour control were included to correlate immune profiles and clinical responses. Results: Anti-angiogenic naïve SFT lesions were heavily infiltrated by CD163+CD14+CD68− and CD163+CD14−CD68− myeloid cells but devoid of T cells. Conversely, post-SM tumours acquired a new subset of CD68+CD14+ myeloid cells and displayed traits of an on-going adaptive immunity, strongly enriched in activated CD8+ and CD4+ T cells. These changes at the tumour site paralleled the alleviation of systemic immunosuppression and the drop in the frequency of circulating monocytic MDSCs (mMDSCs) and granulocytic MDSCs (gMDSCs). Rebound in the number of mMDSCs, but not of gMDSCs occurred at disease progression, and a reduced percentages of mMDSCs, comparable to those found in healthy donors (HDs), endured only in the SM-responsive patients. Conclusions: The immune contexture of SFT patients is heavily involved in anti-angiogenic therapy and it could be exploited to achieve more durable disease control through immune-based combination strategies.
- Published
- 2014
32. Immunogenicity of the ALLAVGATK (gp10017 – 25) peptide in HLA-A3.1 melanoma patients
- Author
-
Chiara Castelli, Gianfrancesco Gallino, Arabella Mazzocchi, Francesca Rini, Giorgio Parmiani, Michele Maio, Licia Rivoltini, Paolo Tarsini, and Filiberto Belli
- Subjects
Tumor-infiltrating lymphocytes ,business.industry ,Melanoma ,T cell ,Immunogenicity ,medicine.medical_treatment ,Immunology ,chemical and pharmacologic phenomena ,Immunotherapy ,medicine.disease ,Peripheral blood mononuclear cell ,Tumor antigen ,Epitope ,medicine.anatomical_structure ,medicine ,Immunology and Allergy ,business ,neoplasms - Abstract
A T cell line recognizing autologous and allogeneic HLA-A3.1 melanomas was obtained from a disease-free melanoma patient (patient 15392). By transfection of a tumor cDNA library and in vitro sensitization experiments, the ALLAVGATK gp100/Mel17-derived peptide was found to be the epitope recognized by this melanoma-specific T cell line. The role of the ALLAVGATK peptide in the systemic immune response to melanoma of this patient was evaluated. When pulsed on the autologous peripheral blood mononuclear cells, the ALLAVGATK peptide generated tumor-specific HLA-A3-restricted T lymphocytes and a single restimulation in vitro was sufficient to raise gp100-specific T lymphocytes, indicating a high frequency of epitope-specific T cells. gp100-specific T cells were also induced from T lymphocytes purified from tumor-invaded lymph nodes (tumor-associated lymphocytes, TAL). TAL-derived effectors displayed lower peptide affinity and lower tumor recognition than effectors elicited from peripheral blood lymphocytes (PBL). To further evaluate its immunogenicity, ALLAVGATK was used to stimulate PBL derived from six additional HLA-A3.1 melanoma patients and seven healthy donors. After 7 weeks of peptide stimulation in vitro the generation of anti-gp100 and tumor-specific T cell lines was achieved in one out of the six patients analyzed. Taken together these data indicate that an in vivo priming leading to a systemic immunity against gp100 in HLA-A3 melanoma patients may occasionally occur and that the immunogenicity of ALLAVGATK peptide in melanoma patients is comparable to that of other HLA-A2-restricted epitopes derived from gp100/Mel 17 protein.
- Published
- 1998
33. Biological quality control for extracorporeal photochemotherapy: Assessing mononuclear cell apoptosis levels in ECP bags of chronic GvHD patients
- Author
-
Francesca, Taverna, Paola, Coluccia, Flavio, Arienti, Annalisa, Birolini, Laura, Terranova, Arabella, Mazzocchi, Francesca, Rini, Luigi, Mariani, Cecilia, Melani, and Fernando, Ravagnani
- Subjects
Adult ,Male ,Quality Control ,Transplantation Conditioning ,Ultraviolet Rays ,Graft vs Host Disease ,Reproducibility of Results ,Apoptosis ,Cell Separation ,Middle Aged ,Flow Cytometry ,Lymphoma, T-Cell, Cutaneous ,Kinetics ,Photopheresis ,Blood Component Removal ,Leukocytes, Mononuclear ,Humans ,Methoxsalen ,Female ,Leukapheresis ,Lymphocytes ,Aged ,Cell Proliferation - Abstract
Extracorporeal photochemotherapy (ECP) is a treatment approved by the FDA for cutaneous T-cell lymphoma, and it is currently used off-label for graft-versus-host disease (GvHD) and other conditions. In agreement with good practices for the therapeutic use of human cells, quality control has to be performed to validate the ECP procedure with the off-line technique. Since no gold-standard biological test is available, we assessed the apoptosis generated in the ECP bag using a flow cytometric analysis. Thirty-one ECP procedures performed on 13 patients with chronic GvHD were studied by monitoring the induction of mononuclear cell (MNC) apoptosis using annexin V/propidium iodide double staining; residual lymphocyte proliferation to standard mitogens was also measured in 17 of the procedures. The kinetics of apoptosis was analyzed at different times in MNCs untreated or treated with 8-methoxy-psoralen plus ultraviolet A; the variation (ΔAPOPTOSIS ) after 24 h revealed the efficacy of the treatment. In 88.6% of the 31 ECP procedures, ΔAPOPTOSIS was15% (the "alerting" threshold for ΔAPOPTOSIS was set at 15% on the basis of our data); in the remainder (19.4%), the increment in apoptosis was lower. In four procedures, the proliferation assay was useful for assessing the effect of ECP on the apheretic bag. In conclusion, both flow cytometric assays enabled a biologically significant result to be obtained. In our opinion, the apoptosis test-being faster and easier than the proliferation test-could be a reliable way to validate ECP procedures.
- Published
- 2013
34. LAG-3 expression defines a subset of CD4(+)CD25(high)Foxp3(+) regulatory T cells that are expanded at tumor sites
- Author
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Licia Rivoltini, Chiara Camisaschi, Filiberto Belli, Annamaria De Filippo, Chiara Casati, Francesca Rini, Michela Perego, Chiara Castelli, Frédéric Triebel, and Giorgio Parmiani
- Subjects
Regulatory T cell ,Immunology ,chemical and pharmacologic phenomena ,Cell Separation ,Biology ,Lymphocyte Activation ,T-Lymphocytes, Regulatory ,Interleukin 21 ,Lymphocytes, Tumor-Infiltrating ,Antigens, CD ,T-Lymphocyte Subsets ,Neoplasms ,medicine ,Immunology and Allergy ,Cytotoxic T cell ,Humans ,IL-2 receptor ,Antigen-presenting cell ,ZAP70 ,FOXP3 ,hemic and immune systems ,Forkhead Transcription Factors ,Natural killer T cell ,Flow Cytometry ,Molecular biology ,Lymphocyte Activation Gene 3 Protein ,medicine.anatomical_structure - Abstract
Human natural regulatory CD4+ T cells comprise 5–10% of peripheral CD4+T cells. They constitutively express the IL-2Rα−chain (CD25) and the nuclear transcription Foxp3. These cells are heterogeneous and contain discrete subsets with distinct phenotypes and functions. Studies in mice report that LAG-3 has a complex role in T cell homeostasis and is expressed in CD4+CD25+ T regulatory cells. In this study, we explored the expression of LAG-3 in human CD4+ T cells and found that LAG-3 identifies a discrete subset of CD4+CD25highFoxp3+ T cells. This CD4+CD25highFoxp3+LAG-3+ population is preferentially expanded in the PBMCs of patients with cancer, in lymphocytes of tumor-invaded lymph nodes and in lymphocytes infiltrating visceral metastasis. Ex vivo analysis showed that CD4+CD25highFoxp3+LAG-3+ T cells are functionally active cells that release the immunosuppressive cytokines IL-10 and TGF-β1, but not IL-2. An in vitro suppression assay using CD4+CD25highLAG-3+ T cells sorted from in vitro expanded CD4+CD25high regulatory T cells showed that this subset of cells is endowed with potent suppressor activity that requires cell-to-cell contact. Our data show that LAG-3 defines an active CD4+CD25highFoxp3+ regulatory T cell subset whose frequency is enhanced in the PBMCs of patients with cancer and is expanded at tumor sites.
- Published
- 2010
35. Soluble human LAG-3 molecule amplifies the in vitro generation of type 1 tumor-specific immunity
- Author
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Chiara Camisaschi, Chiara Castelli, Francesca Rini, Licia Rivoltini, Frédéric Triebel, Flavio Arienti, Giorgio Parmiani, and Chiara Casati
- Subjects
Cancer Research ,medicine.medical_treatment ,Antigen-Presenting Cells ,Epitopes, T-Lymphocyte ,CHO Cells ,Biology ,CD8-Positive T-Lymphocytes ,Lymphocyte Activation ,Epitope ,Interferon-gamma ,Immune system ,MART-1 Antigen ,Antigen ,Adjuvants, Immunologic ,Antigens, CD ,Antigens, Neoplasm ,Cricetinae ,medicine ,Cytotoxic T cell ,Animals ,Humans ,Interferon gamma ,Antigen-presenting cell ,Melanoma ,Lymphocyte Activation Gene 3 Protein ,Recombinant Proteins ,Neoplasm Proteins ,Cytokine ,Oncology ,Immunoglobulin G ,Immunology ,Cancer research ,Cytokines ,Colorectal Neoplasms ,Peptides ,CD8 ,medicine.drug ,T-Lymphocytes, Cytotoxic - Abstract
The adjuvant activities of the human lymphocyte activation gene-3 (LAG-3) molecule have been evaluated in a human setting by investigating the ability of a soluble recombinant human LAG-3 protein (hLAG-3Ig) to enhance the in vitro induction of viral- and tumor-specific CTLs. We found that soluble human LAG-3 significantly sustained the generation and expansion of influenza matrix protein Melan-A/MART-1 and survivin-specific CD8+ T lymphocytes in peripheral blood mononuclear cells (PBMC) of both cancer patients and healthy donors, showing its ability to boost CD8+ T-cell memory response or to prime naive T cells in vitro. The peptide-specific T cells generated in the presence of hLAG-3Ig were endowed with cytotoxic activity and enhanced release of type 1 cytotoxic T (Tc1) cytokines and were able to recognize tumor cells expressing their nominal antigen. Phenotype and cytokine/chemokines produced by antigen-presenting cells (APC) of PBMCs exposed in vitro for 2 days to peptide and hLAG-3Ig indicate that the LAG-3–mediated adjuvant effect may depend on a direct activation of circulating APCs. Our data revealed the activity of hLAG-3Ig in inducing tumor-associated, antigen-specific CD8+ T-cell responses in a human setting and strongly support the conclusion that this recombinant protein is a potential candidate adjuvant for cancer vaccines. (Cancer Res 2006; 66(8): 4450-60)
- Published
- 2006
36. Heat shock proteins: biological functions and clinical application as personalized vaccines for human cancer
- Author
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Chiara Castelli, Alessandro Testori, Vincenzo Mazzaferro, Michele Maio, Filiberto Belli, Giorgio Parmiani, Francesca Rini, Pramod K. Srivastava, Licia Rivoltini, and Jorgelina Coppa
- Subjects
Cancer Research ,Colorectal cancer ,Immunology ,Cell ,Antigen presentation ,Antigen-Presenting Cells ,Cancer Vaccines ,Heat shock protein ,medicine ,Humans ,Immunology and Allergy ,HSP70 Heat-Shock Proteins ,Heat-Shock Proteins ,Antigen Presentation ,biology ,business.industry ,Melanoma ,Vaccination ,Membrane Proteins ,medicine.disease ,Endocytosis ,Hsp70 ,Cell biology ,medicine.anatomical_structure ,Oncology ,Chaperone (protein) ,biology.protein ,business ,Intracellular - Abstract
Heat shock proteins (HSPs) are a large family of proteins with different molecular weights and different intracellular localizations. These proteins undertake crucial functions in maintaining cell homeostasis, and therefore they have been conserved during evolution. Hsp70 and Grp94/gp96, due to their peptide chaperone capacity and their ability to actively interact with professional antigen-presenting cells (APCs), are also endowed with crucial immunological functions. The immunological properties of these proteins and their implications for vaccine in human cancer will be discussed. Immunological and clinical data of phase I/II studies in melanoma and colorectal cancer patients will be reviewed.
- Published
- 2004
37. The apoptosis inhibitor protein survivin induces tumor-specific CD8+ and CD4+ T cells in colorectal cancer patients
- Author
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Chiara, Casati, Piero, Dalerba, Licia, Rivoltini, Gianfrancesco, Gallino, Paola, Deho, Francesca, Rini, Filiberto, Belli, Delia, Mezzanzanica, Aurora, Costa, Salvatore, Andreola, Ermanno, Leo, Giorgio, Parmiani, and Chiara, Castelli
- Subjects
CD4-Positive T-Lymphocytes ,Male ,Survivin ,Epitopes, T-Lymphocyte ,CD8-Positive T-Lymphocytes ,Middle Aged ,Transfection ,Peptide Fragments ,Inhibitor of Apoptosis Proteins ,Neoplasm Proteins ,HLA-A2 Antigen ,Tumor Cells, Cultured ,Humans ,Female ,Amino Acid Sequence ,Colorectal Neoplasms ,Microtubule-Associated Proteins ,Aged - Abstract
The identification of tumor-associated antigens expressed by colorectal carcinoma remains one of the major goals for designing novel immunological treatments for this tumor. By using a reverse-immunology approach, we show here that the inhibitor of apoptosis protein, survivin, is immunogenic in colorectal cancer patients. In particular, we found that survivin elicited CD8(+) T cell-mediated responses in peripheral blood or in tumor-associated lymphocytes from patients at different disease stage. Colorectal carcinoma cells were recognized by survivin-specific T lymphocytes, and the survivin-specific, class-I HLA-restricted T lymphocytes were fully activated and released interleukin-2 in response to HLA/survivin-peptide complexes expressed by tumor cells. In addition to CD8-mediated responses, survivin specifically stimulated CD4+ T-cell reactivity in peripheral blood lymphocytes from the same patients, thus suggesting that a complete activation of the immune system may occur in response to this antiapoptotic protein. These findings indicate that survivin could be considered a valuable tumor-associated antigen for immune-based clinical approaches in colorectal cancer.
- Published
- 2003
38. Quantification of fibrosis in chronic hepatitis C: Performance of Transient Elastography and Acoustic Radiation Force Impulse using Collagen Proportionate Area as reference
- Author
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C. Cammà, Vincenza Calvaruso, Antonio Craxì, N. Alessi, Fabrizio Bronte, V. Di Marco, Francesca Rini, and M.G. Bavetta
- Subjects
medicine.medical_specialty ,Hepatology ,Chronic hepatitis ,business.industry ,Fibrosis ,Gastroenterology ,Medicine ,Radiology ,Impulse (physics) ,business ,Transient elastography ,medicine.disease ,Acoustic radiation force - Published
- 2014
39. T cell responses in colorectal cancer patients: evidence for class II HLA-restricted recognition of shared tumor-associated antigens
- Author
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Francesco Gallino, Claudia Lombardo, Giorgio Parmiani, Salvatore Andreola, Andreas J.A. Bremers, Chiara Castelli, Francesca Rini, Filiberto Belli, Peter J. K. Kuppen, and Ermanno Leo
- Subjects
Cancer Research ,Immunity, Cellular ,business.industry ,Colorectal cancer ,Antigen processing ,T cell ,Monocyte ,T-Lymphocytes ,Histocompatibility Antigens Class II ,Cancer ,Epitopes, T-Lymphocyte ,Human leukocyte antigen ,Dendritic Cells ,medicine.disease ,medicine.anatomical_structure ,Immune system ,Oncology ,Antigen ,Antigens, Neoplasm ,Immunology ,Medicine ,Humans ,business ,Colorectal Neoplasms - Abstract
Few cases of anti-colon cancer specific T lymphocytes have been described so far. Moreover, the majority of these effectors were generated in vitro by stimulating PBMC from patients or healthy donors with peptides that were derived from proteins expressed and/or secreted by colon cancer tissue such as CEA, Mucin or Her-2/neu. The aim of our study was to evaluate the immunogenicity of colorectal carcinomas in an autologous setting. We exploited the antigen processing and presentation capacity of dendritic cells (DC) to establish an in vitro autologous system that can bypass the need of obtaining cultured tumor cells. DC were generated from the adherent monocyte fraction of PBMC taken from stage II/III colorectal cancer patients. A single cell suspension was prepared by mechanical and enzymatic disruption of the surgical specimens immediately after resection. DC were loaded with autologous tumor lysate, obtained by repeated freezing and thawing, before being used as stimulators for autologous PBL. HLA-class II restricted T cells that recognize the autologous tumor could be generated in a proportion of patients. The fine specificity of the anti-tumor T cells indicates that differentiation as well as tumor restricted antigens are expressed in colon cancer and that these antigens can evoke a class II HLA-restricted response in an autologous setting. Altogether these findings may open a new perspective for a DC based vaccination of colon cancer patients. Int. J. Cancer 88:956–961, 2000. © 2000 Wiley-Liss, Inc.
- Published
- 2000
40. LAG-3 expression and role in human pDC biology
- Author
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Chiara, Camisaschi, primary, Annamaria, De Filippo, primary, Valeria, Beretta, primary, Francesca, Rini, primary, Marcella, Tazzari, primary, Flavio, Arienti, primary, Fredric, Triebel, primary, Licia, Rivoltini, primary, and Chiara, Castelli, primary
- Published
- 2013
- Full Text
- View/download PDF
41. Identification of a mutated receptor-like protein tyrosine phosphatase κ as a novel, class II HLA-restricted melanoma antigen
- Author
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Licia Rivoltini, Angela Greco, Paola Deho, Paul F. Robbins, Arabella Mazzocchi, Giorgio Parmiani, Paola Squarcina, Chiara Castelli, Luisa Novellino, Nicolina Renkvist, and Francesca Rini
- Subjects
CD4-Positive T-Lymphocytes ,medicine.medical_treatment ,T cell ,Immunology ,Molecular Sequence Data ,Epitopes, T-Lymphocyte ,Human leukocyte antigen ,Biology ,Transfection ,Epitope ,Interleukin 21 ,Immune system ,Lymphocytes, Tumor-Infiltrating ,Antigens, Neoplasm ,medicine ,Tumor Cells, Cultured ,Immunology and Allergy ,Cytotoxic T cell ,Humans ,IL-2 receptor ,Amino Acid Sequence ,RNA, Messenger ,Melanoma ,Cell Line, Transformed ,Antigen Presentation ,Histocompatibility Antigens Class II ,Receptor-Like Protein Tyrosine Phosphatases, Class 2 ,Immunotherapy ,HLA-DR Antigens ,Molecular biology ,Peptide Fragments ,Clone Cells ,Antigens, Differentiation, B-Lymphocyte ,medicine.anatomical_structure ,Mutation ,Protein Tyrosine Phosphatases - Abstract
Recent studies increasingly point to a pivotal role of CD4+ T cells in human anti-tumor immune response. Here we show that lymphocytes purified from a tumor-infiltrated lymph node of a melanoma patient that had remained disease free for 10 years after surgical resection of a lymph node metastasis comprised oligoclonal class II HLA-restricted CD4+ T cells recognizing the autologous tumor cells in vitro. In fact, the CD4+ T cell clones isolated from these lymphocytes displayed a tumor-specific, cytotoxic activity in addition to a Th1-like cytokine profile. By a genetic approach, a peptide derived from a mutated receptor-like protein tyrosine phosphatase κ was identified as a novel HLA-DR10-restricted epitope for all the melanoma-specific CD4+ T cell clones. The immunogenic peptide was shown to contain the mutated residue that was crucial for T cell recognition and activation. Moreover, a systemic immunity against the mutated peptide was detectable in the patient’s peripheral blood T lymphocytes obtained during the disease-free period of follow-up. These findings further support the relevance of CD4+ T cells directed against mutated epitopes in tumor immunity and provide the rationale for a possible usage of mutated, tumor-specific Ags for immunotherapy of human cancer.
42. Recognition of melanoma-derived antigens by CTL: Possible mechanisms involved in down-regulating anti-tumor T-cell reactivity
- Author
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Ettore Appella, Alessandro Borsatti, Paola Squarcina, Giorgio Parmiani, Douglas J. Loftus, Licia Rivoltini, Francesca Rini, Filiberto Belli, Chiara Castelli, Carsten Geisler, Francesco M. Marincola, and Flavio Arienti
- Subjects
Polymers and Plastics ,medicine.medical_treatment ,T-Lymphocytes ,Down-Regulation ,Epitopes, T-Lymphocyte ,Peptide ,Biology ,Cancer Vaccines ,Epitope ,Epitopes ,MART-1 Antigen ,Antigen ,In vivo ,Antigens, Neoplasm ,HLA-A2 Antigen ,medicine ,Humans ,Antigens, Viral ,Melanoma ,HLA-A1 Antigen ,General Environmental Science ,chemistry.chemical_classification ,Vaccination ,Immunotherapy ,medicine.disease ,Neoplasm Proteins ,CTL ,Immunization ,chemistry ,Immunology ,Peptides ,T-Lymphocytes, Cytotoxic - Abstract
Several T cell-recognized epitopes presented by melanoma cells have been identified recently. Despite the large array of epitopes potentially available for clinical use, it is still unclear which of these antigens could be effective in mediating anti-tumor responses when used as a vaccine. Preliminary studies showed that immunization of melanoma patients with epitopes derived from proteins of the MAGE family may result in significant clinical regressions. However, no sign of systemic immunization could be observed in peripheral blood of treated patients. Conversely, significant immunization (detected as increased antigen-specific CTL activity in peripheral blood) was obtained by vaccinating HLA-A2.1+ melanoma patients with the immunodominant epitope (residues 27-35) of the differentiation antigen MART-1, but this immunization was not accompanied by a significant clinical response. To implement immunotherapeuties capable of significantly impacting disease outcome, it is necessary to identify the potential mechanisms responsible for the failure of some antigens to mediate significant anti-tumor responses in vivo. In the case of the MART-1(27-35) epitope, we hypothesize that one of these mechanisms may be related to the existence of natural analogs of this peptide in other human normal proteins.
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