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Article: Vinorelbine and Intermittent Cyclophosphamide Sensitize an Aggressive Myc-Driven B-Cell Lymphoma to Anti-PD-1 by an Immunological Memory Effective against Tumor Re-Challenge.

Orecchioni, Stefania / Falvo, Paolo / Talarico, Giovanna / Mitola, Giulia / Bravetti, Giulia / Mancuso, Patrizia / Nicoli, Paola / Bertolini, Francesco

Journal of clinical medicine

2023 Volume 12, Issue 7

Abstract: We have previously shown in triple-negative breast cancer (TNBC) models that a triple therapy (TT) including intermittent cyclophosphamide (C), vinorelbine (V), and anti-PD-1 activates antigen-presenting cells (APC) and generates stem like-T cells able ... ...

Abstract	We have previously shown in triple-negative breast cancer (TNBC) models that a triple therapy (TT) including intermittent cyclophosphamide (C), vinorelbine (V), and anti-PD-1 activates antigen-presenting cells (APC) and generates stem like-T cells able to control local and metastatic tumor progression. In the present manuscript, we report the generation of a highly aggressive, anti-PD-1 resistant model of a high-grade, Myc-driven B-cell non-Hodgkin's lymphoma (NHL) that can be controlled in vivo by TT but not by other chemotherapeutic agents, including cytarabine (AraC), platinum (P), and doxorubicin (D). The immunological memory elicited in tumor-bearing mice by TT (but not by other treatments) can effectively control NHL re-challenge even at very high inoculum doses. TT re-shaped the landscape of circulating innate NK cells and adaptive immune cells, including B and T cells, and significantly reduced exhausted CD4
Language	English
Publishing date	2023-03-27
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm12072535
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Article ; Online: Vinorelbine and Intermittent Cyclophosphamide Sensitize an Aggressive Myc-Driven B-Cell Lymphoma to Anti-PD-1 by an Immunological Memory Effective against Tumor Re-Challenge

Stefania Orecchioni / Paolo Falvo / Giovanna Talarico / Giulia Mitola / Giulia Bravetti / Patrizia Mancuso / Paola Nicoli / Francesco Bertolini

Journal of Clinical Medicine, Vol 12, Iss 2535, p

2023 Volume 2535

Abstract	We have previously shown in triple-negative breast cancer (TNBC) models that a triple therapy (TT) including intermittent cyclophosphamide (C), vinorelbine (V), and anti-PD-1 activates antigen-presenting cells (APC) and generates stem like-T cells able to control local and metastatic tumor progression. In the present manuscript, we report the generation of a highly aggressive, anti-PD-1 resistant model of a high-grade, Myc-driven B-cell non-Hodgkin’s lymphoma (NHL) that can be controlled in vivo by TT but not by other chemotherapeutic agents, including cytarabine (AraC), platinum (P), and doxorubicin (D). The immunological memory elicited in tumor-bearing mice by TT (but not by other treatments) can effectively control NHL re-challenge even at very high inoculum doses. TT re-shaped the landscape of circulating innate NK cells and adaptive immune cells, including B and T cells, and significantly reduced exhausted CD4 + and CD8 + TIM3 + PD-1 + T cells in the spleens of treated mice.
Keywords	lymphoma ; cyclophosphamide ; vinorelbine ; metronomic chemotherapy ; checkpoint inhibitors ; Medicine ; R
Subject code	333
Language	English
Publishing date	2023-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article: A single-cell transcriptomic landscape of innate and adaptive intratumoral immunity in triple negative breast cancer during chemo- and immunotherapies.

Carpen, Laura / Falvo, Paolo / Orecchioni, Stefania / Mitola, Giulia / Hillje, Roman / Mazzara, Saveria / Mancuso, Patrizia / Pileri, Stefano / Raveane, Alessandro / Bertolini, Francesco

Cell death discovery

2022 Volume 8, Issue 1, Page(s) 106

Abstract: Breast cancer (BC) constitutes a major health problem worldwide, making it the most common malignancy in women. Current treatment options for BC depend primarily on histological type, molecular markers, clinical aggressiveness and stage of disease. ... ...

Abstract	Breast cancer (BC) constitutes a major health problem worldwide, making it the most common malignancy in women. Current treatment options for BC depend primarily on histological type, molecular markers, clinical aggressiveness and stage of disease. Immunotherapy, such as αPD-1, have shown combinatorial clinical activity with chemotherapy in triple negative breast cancer (TNBC) delineating some therapeutic combinations as more effective than others. However, a clear overview of the main immune cell populations involved in these treatments has never been provided.Here, an assessment of the immune landscape in the tumor microenvironment (TME) of two TNBC mouse models has been performed using single-cell RNA sequencing technology. Specifically, immune cells were evaluated in untreated conditions and after treatments with chemotherapy or immunotherapy used as single agents or in combination. A decrease of Treg was found in treatments with in vivo efficacy as well as γδ T cells, which have a pro-tumoral activity in mice. Focusing on Cd8 T cells, across all the conditions, a general increase of exhausted-like Cd8 T cells was confirmed in pre-clinical treatments with low efficacy and an opposite trend was found for the proliferative Cd8 T cells. Regarding macrophages, M2-like cells were enriched in treatments with low efficacy while M1-like macrophages followed an opposite trend. For both models, similar proportions of B cells were detected with an increase of proliferative B cells in treatments involving cisplatin in combination with αPD-1. The fine-scale characterization of the immune TME in this work can lead to new insights on the diagnosis and treatment of TNBC.
Language	English
Publishing date	2022-03-08
Publishing country	United States
Document type	Journal Article
ISSN	2058-7716
ISSN	2058-7716
DOI	10.1038/s41420-022-00893-x
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Article: Diagnostic Performance and Cell Count of EBUS-TBNA Needle Gauges: A Prospective Trial.

Guarize, Juliana / Diotti, Cristina / Casiraghi, Monica / Donghi, Stefano / Di Tonno, Clementina / Mancuso, Patrizia / Zorzino, Laura / Sedda, Giulia / Radice, Davide / Bertolaccini, Luca / Spaggiari, Lorenzo

Journal of clinical medicine

2023 Volume 12, Issue 12

Abstract: Background: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a well-established diagnostic procedure for evaluating hilar and mediastinal lymphadenopathies and is the gold standard for lung cancer diagnosis and staging. ... ...

Abstract	Background: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a well-established diagnostic procedure for evaluating hilar and mediastinal lymphadenopathies and is the gold standard for lung cancer diagnosis and staging. Recent studies assessed the effectiveness of the 19-G flex needle in obtaining larger EBUS-TBNA samples, and prospective small series gave similar results in terms of diagnostic yield when testing different gauge needles. The lack of homogeneity between series and the small sample size of some prospective cohorts poses a limit to the validity of those results. This prospective controlled study compared the 19-G flex and 22-G needles in terms of diagnostic yield. An objective laboratory method was used to count cells and compare the two needles' cytologic yields. Material: A prospective controlled study was conducted on 90 patients undergoing EBUS-TBNA for the diagnosis of hilar and mediastinal lymphadenopathies. The institutional ethic committee (IEO573) approved the study, and informed consent was obtained from all patients. Results: A total of 90 patients were enrolled in this study, 84.4% of whom were diagnosed with malignancy and 15.6% with non-neoplastic disease. Sensitivity for malignancy was 93.4% (CI: 87.4-97.1%) for the 19-G needle and 92.6% (CI: 86.3-96.5%) for the 22-G needle ( Conclusions: The 19-G flex EBUS-TBNA needle is comparable to the 22-G needle in terms of diagnostic yield for cyto-histological evaluation of hilar and mediastinal lymphadenopathies. There is no difference between the 19-G and 22-G needle cell counts evaluated by flow cytometry.
Language	English
Publishing date	2023-06-13
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm12124033
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Article ; Online: Diagnostic Performance and Cell Count of EBUS–TBNA Needle Gauges

Juliana Guarize / Cristina Diotti / Monica Casiraghi / Stefano Donghi / Clementina Di Tonno / Patrizia Mancuso / Laura Zorzino / Giulia Sedda / Davide Radice / Luca Bertolaccini / Lorenzo Spaggiari

Journal of Clinical Medicine, Vol 12, Iss 4033, p

A Prospective Trial

2023 Volume 4033

Abstract: Background. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a well-established diagnostic procedure for evaluating hilar and mediastinal lymphadenopathies and is the gold standard for lung cancer diagnosis and staging. ... ...

Abstract	Background. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a well-established diagnostic procedure for evaluating hilar and mediastinal lymphadenopathies and is the gold standard for lung cancer diagnosis and staging. Recent studies assessed the effectiveness of the 19-G flex needle in obtaining larger EBUS-TBNA samples, and prospective small series gave similar results in terms of diagnostic yield when testing different gauge needles. The lack of homogeneity between series and the small sample size of some prospective cohorts poses a limit to the validity of those results. This prospective controlled study compared the 19-G flex and 22-G needles in terms of diagnostic yield. An objective laboratory method was used to count cells and compare the two needles’ cytologic yields. Material. A prospective controlled study was conducted on 90 patients undergoing EBUS-TBNA for the diagnosis of hilar and mediastinal lymphadenopathies. The institutional ethic committee (IEO573) approved the study, and informed consent was obtained from all patients. Results. A total of 90 patients were enrolled in this study, 84.4% of whom were diagnosed with malignancy and 15.6% with non-neoplastic disease. Sensitivity for malignancy was 93.4% (CI: 87.4–97.1%) for the 19-G needle and 92.6% (CI: 86.3–96.5%) for the 22-G needle ( p = 0.80). The percentage of malignant cells in the cell block was 63.9% and 61.5% for the 22-G and 19-G needles, respectively. The cell count assessed by flow cytometry was 2071 cells/µL (IQR: 600,2265) with the 22-G needle and 2761 cells/µL (IQR: 505,3250) with the 19-G needle ( p = 0.79). The malignant cell count was 0.05 × 10 3 cells/µL with the 22-G and 0.08 × 10 3 cells/µL with the 19-G needle ( p = 0.70). There was no difference in the presence of tissue cores in the samples, and rapid on-site evaluation (ROSE) cellularity was comparable between the two needles. Conclusions. The 19-G flex EBUS-TBNA needle is comparable to the 22-G needle in terms of diagnostic yield for ...
Keywords	endobronchial ultrasound-GUIDED transbronchial needle aspiration ; 19-G flex needle ; diagnostic yield ; cell count ; lung cancer ; Medicine ; R
Subject code	610
Language	English
Publishing date	2023-06-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Dampening of cytotoxic innate lymphoid cells: A new tumour immune escape mechanism in B cell non-Hodgkin's lymphoma.

Roma, Stefania / Camisaschi, Chiara / Mancuso, Patrizia / Trabanelli, Sara / Vanazzi, Anna / Villa, Stefania / Prati, Daniele / Fiori, Stefano / Lorenzini, Daniele / Tabanelli, Valentina / Pileri, Stefano / Tarella, Corrado / Jandus, Camilla / Bertolini, Francesco

Cellular immunology

2022 Volume 382, Page(s) 104615

Abstract: The role and regulation of innate immune cells is poorly understood in B-cell non-Hodgkin lymphoma (NHL). As natural killer (NK) cells, helper innate lymphoid cells (ILCs) are lymphocytes endowed with either anti- or pro-tumour activity and involved in ... ...

Abstract	The role and regulation of innate immune cells is poorly understood in B-cell non-Hodgkin lymphoma (NHL). As natural killer (NK) cells, helper innate lymphoid cells (ILCs) are lymphocytes endowed with either anti- or pro-tumour activity and involved in inflammatory processes. In our ex vivo analysis of NK cells and ILCs from NHL patients, we observed that, in comparison to healthy donors (HD), the frequency of the cytotoxic subset of NK cells, the CD16
MeSH term(s)	Humans ; Tumor Escape ; Immunity, Innate ; Lymphocytes ; Killer Cells, Natural ; Antineoplastic Agents ; Neoplasms/pathology ; Lymphoma, Non-Hodgkin/pathology
Chemical Substances	Antineoplastic Agents
Language	English
Publishing date	2022-09-27
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	80094-6
ISSN	1090-2163 ; 0008-8749
ISSN (online)	1090-2163
ISSN	0008-8749
DOI	10.1016/j.cellimm.2022.104615
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Article ; Online: Efficacy of venetoclax based salvage chemotherapy followed by "Minimal Residual Disease driven"-venetoclax maintenance therapy post-allotransplant in a young patient with high risk primary refractory acute myeloid leukemia.

Todisco, Elisabetta / Gigli, Federica / Sammassimo, Simona / Camisaschi, Chiara / Mancuso, Patrizia / Ronchini, Chiara / Ramadan, Safaa / Bertolini, Francesco / Pastano, Rocco / Tarella, Corrado

Leukemia & lymphoma

2020 Volume 61, Issue 9, Page(s) 2277–2279

MeSH term(s)	Bridged Bicyclo Compounds, Heterocyclic/therapeutic use ; Humans ; Leukemia, Myeloid, Acute/drug therapy ; Neoplasm, Residual ; Sulfonamides/therapeutic use
Chemical Substances	Bridged Bicyclo Compounds, Heterocyclic ; Sulfonamides ; venetoclax (N54AIC43PW)
Language	English
Publishing date	2020-05-02
Publishing country	United States
Document type	Letter
ZDB-ID	1042374-6
ISSN	1029-2403 ; 1042-8194
ISSN (online)	1029-2403
ISSN	1042-8194
DOI	10.1080/10428194.2020.1759049
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Article ; Online: Cyclophosphamide and Vinorelbine Activate Stem-Like CD8

Falvo, Paolo / Orecchioni, Stefania / Hillje, Roman / Raveane, Alessandro / Mancuso, Patrizia / Camisaschi, Chiara / Luzi, Lucilla / Pelicci, PierGiuseppe / Bertolini, Francesco

Cancer research

2020 Volume 81, Issue 3, Page(s) 685–697

Abstract: Checkpoint inhibitors (CI) instigate anticancer immunity in many neoplastic diseases, albeit only in a fraction of patients. The clinical success of cyclophosphamide (C)-based haploidentical stem-cell transplants indicates that this drug may re- ... ...

Abstract	Checkpoint inhibitors (CI) instigate anticancer immunity in many neoplastic diseases, albeit only in a fraction of patients. The clinical success of cyclophosphamide (C)-based haploidentical stem-cell transplants indicates that this drug may re-orchestrate the immune system. Using models of triple-negative breast cancer (TNBC) with different intratumoral immune contexture, we demonstrate that a combinatorial therapy of intermittent C, CI, and vinorelbine activates antigen-presenting cells (APC), and abrogates local and metastatic tumor growth by a T-cell-related effect. Single-cell transcriptome analysis of >50,000 intratumoral immune cells after therapy treatment showed a gene signature suggestive of a change resulting from exposure to a mitogen, ligand, or antigen for which it is specific, as well as APC-to-T-cell adhesion. This transcriptional program also increased intratumoral Tcf1
MeSH term(s)	Animals ; Antigen-Presenting Cells/drug effects ; Antigen-Presenting Cells/immunology ; Antineoplastic Agents/pharmacology ; Antineoplastic Combined Chemotherapy Protocols/pharmacology ; CD8-Positive T-Lymphocytes/drug effects ; CD8-Positive T-Lymphocytes/immunology ; Cell Adhesion ; Cyclophosphamide/pharmacology ; Female ; Hepatocyte Nuclear Factor 1-alpha/metabolism ; Immune Checkpoint Inhibitors/pharmacology ; Immunity, Cellular ; Mice ; Mice, Inbred BALB C ; Programmed Cell Death 1 Receptor/antagonists & inhibitors ; Transcriptome ; Triple Negative Breast Neoplasms/drug therapy ; Triple Negative Breast Neoplasms/genetics ; Triple Negative Breast Neoplasms/immunology ; Vinorelbine/pharmacology
Chemical Substances	Antineoplastic Agents ; Hepatocyte Nuclear Factor 1-alpha ; Hnf1a protein, mouse ; Immune Checkpoint Inhibitors ; Programmed Cell Death 1 Receptor ; Cyclophosphamide (8N3DW7272P) ; Vinorelbine (Q6C979R91Y)
Language	English
Publishing date	2020-12-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1432-1
ISSN	1538-7445 ; 0008-5472
ISSN (online)	1538-7445
ISSN	0008-5472
DOI	10.1158/0008-5472.CAN-20-1818
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Article ; Online: A prospective, multicenter study on hematopoietic stem-cell mobilization with cyclophosphamide plus granulocyte colony-stimulating factor and 'on-demand' plerixafor in multiple myeloma patients treated with novel agents.

Mina, Roberto / Petrucci, Maria Teresa / Bonello, Francesca / Bongarzoni, Velia / Saccardi, Riccardo / Bertuglia, Giuseppe / Mengarelli, Andrea / Spadaro, Andrea / Lisi, Chiara / Curci, Paola / Lemoli, Roberto Massimo / Ballanti, Stelvio / Floris, Rita / Cupelli, Luca / Tosi, Patrizia / Olivieri, Attilio / Rota-Scalabrini, Delia / Cangialosi, Clotilde / Nozzoli, Chiara /

Anaclerico, Barbara / Fazio, Francesca / Bruno, Benedetto / Mancuso, Katia / Corradini, Paolo / Milone, Giuseppe / Boccadoro, Mario

Haematologica

2023

Abstract: High-dose melphalan plus autologous stem-cell transplantation (ASCT) is a standard of care for transplant-eligible patients with newly diagnosed multiple myeloma (NDMM), and adequate hematopoietic stem-cell (HSC) collection is crucial to ensure ... ...

Abstract	High-dose melphalan plus autologous stem-cell transplantation (ASCT) is a standard of care for transplant-eligible patients with newly diagnosed multiple myeloma (NDMM), and adequate hematopoietic stem-cell (HSC) collection is crucial to ensure hematologic recovery after ASCT. In this prospective, observational study we evaluated HSC mobilization with granulocyte colony-stimulating factor (G-CSF), cyclophosphamide, and 'on-demand' plerixafor (in patients with.
Language	English
Publishing date	2023-11-16
Publishing country	Italy
Document type	Journal Article
ZDB-ID	2333-4
ISSN	1592-8721 ; 0017-6567 ; 0390-6078
ISSN (online)	1592-8721
ISSN	0017-6567 ; 0390-6078
DOI	10.3324/haematol.2023.284023
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Article: About CD45-/CD31+/CD105+ circulating cells in patients with gynecologic malignancies--letter.

Bertolini, Francesco / Mancuso, Patrizia / Heymach, John V

Clinical cancer research : an official journal of the American Association for Cancer Research

2014 Volume 20, Issue 5, Page(s) 1393

MeSH term(s)	Antigens, CD/metabolism ; Endothelial Cells/metabolism ; Female ; Genital Neoplasms, Female/metabolism ; Genital Neoplasms, Female/pathology ; Humans ; Leukocyte Common Antigens/metabolism ; Male ; Platelet Endothelial Cell Adhesion Molecule-1/metabolism ; Receptors, Cell Surface/metabolism
Chemical Substances	Antigens, CD ; Platelet Endothelial Cell Adhesion Molecule-1 ; Receptors, Cell Surface ; Leukocyte Common Antigens (EC 3.1.3.48)
Language	English
Publishing date	2014-03-01
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	1225457-5
ISSN	1557-3265 ; 1078-0432
ISSN (online)	1557-3265
ISSN	1078-0432
DOI	10.1158/1078-0432.CCR-13-2855
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