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1. BNT162b2 vaccine induces antibody release in saliva: a possible role for mucosal viral protection?

Author

Abbass Darwich, Chiara Pozzi, Giulia Fornasa, Michela Lizier, Elena Azzolini, Ilaria Spadoni, Francesco Carli, Antonio Voza, Antonio Desai, Carlo Ferrero, Luca Germagnoli, ICH COVID‐19 Task‐force, Alberto Mantovani, Maria Rescigno, Aghemo Alessio, Anfray Clement, Badalamenti Salvatore, Belgiovine Cristina, Bertocchi Alice, Bombace Sara, Brescia Paola, Calcaterra Francesca, Calvi Michela, Cancellara Assunta, Capucetti Arianna, Carenza Claudia, Carloni Sara, Carnevale Silvia, Cazzetta Valentina, Cecconi Maurizio, Ciccarelli Michele, Coianiz Nicolò, Darwich Abbass, Ana Lleo De Nalda, De Paoli Federica, Di Donato Rachele, Digifico Elisabeth, Durante Barbara, Farina Floriana Maria, Ferrari Valentina, Fornasa Giulia, Franzese Sara, Gil Gomez Antonio, Giugliano Silvia, Ana Rita Gomes, Lizier Michela, Lo Cascio Antonino, Melacarne Alessia, Mozzarelli Alessandro, My Ilaria, Oresta Bianca, Pasqualini Fabio, Pastò Anna, Pelamatti Erica, Perucchini Chiara, Pozzi Chiara, Rimoldi Valeria, Rimoldi Monica, Scarpa Alice, Selmi Carlo, Silvestri Alessandra, Sironi Marina, Spadoni Ilaria, Spano' Salvatore, Spata Gianmarco, Supino Domenico, Tentorio Paolo, Ummarino Aldo, Valentino Sonia, Voza Antonio, Zaghi Elisa, and Zanon Veronica

Subjects
BNT162b2, IgA, IgG, mucosal immunity, SARS‐CoV‐2, Medicine (General), R5-920, Genetics, QH426-470
Abstract

Abstract Vaccination against an airborne pathogen is very effective if it induces also the development of mucosal antibodies that can protect against infection. The mRNA‐based vaccine‐encoding SARS‐CoV‐2 full‐length spike protein (BNT162b2, Pfizer/BioNTech) protects also against infection despite being administered systemically. Here, we show that upon vaccination, cognate IgG molecules are also found in the saliva and are more abundant in SARS‐CoV‐2 previously exposed subjects, paralleling the development of plasma IgG. The antibodies titer declines at 3 months from vaccination. We identified a concentration of specific IgG in the plasma above which the relevant IgG can be detected in the saliva. Regarding IgA antibodies, we found only protease‐susceptible IgA1 antibodies in plasma while they were present at very low levels in the saliva over the course of vaccination of SARS‐CoV‐2‐naïve subjects. Thus, in response to BNT162b2 vaccine, plasma IgG can permeate into mucosal sites and participate in viral protection. It is not clear why IgA1 are detected in low amount, they may be proteolytically cleaved.

Published
2022
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2. A ‘Multiomic’ Approach of Saliva Metabolomics, Microbiota, and Serum Biomarkers to Assess the Need of Hospitalization in Coronavirus Disease 2019

Author

Chiara Pozzi, Riccardo Levi, Daniele Braga, Francesco Carli, Abbass Darwich, Ilaria Spadoni, Bianca Oresta, Carola Conca Dioguardi, Clelia Peano, Leonardo Ubaldi, Giovanni Angelotti, Barbara Bottazzi, Cecilia Garlanda, Antonio Desai, Antonio Voza, Elena Azzolini, Maurizio Cecconi, Alberto Mantovani, Giuseppe Penna, Riccardo Barbieri, Letterio S. Politi, Maria Rescigno, Aghemo Alessio, Anfray Clement, Badalamenti Salvatore, Belgiovine Cristina, Bertocchi Alice, Bombace Sara, Brescia Paola, Calcaterra Francesca, Calvi Michela, Cancellara Assunta, Capucetti Arianna, Carenza Claudia, Carloni Sara, Carnevale Silvia, Cazzetta Valentina, Cecconi Maurizio, Ciccarelli Michele, Coianiz Nicolò, Darwich Abbass, Lleo de Nalda Ana, De Paoli Federica, Di Donato Rachele, Digifico Elisabeth, Durante Barbara, FARINA Floriana Maria, Ferrari Valentina, Fornasa Giulia, Franzese Sara, Gil Gomez Antonio, Giugliano Silvia, Gomes Ana Rita, Lizier Michela, Lo Cascio Antonino, Melacarne Alessia, Mozzarelli Alessandro, My Ilaria, Oresta Bianca, Pasqualini Fabio, Pastò Anna, Pelamatti Erica, Perucchini Chiara, Pozzi Chiara, Rimoldi Valeria, Rimoldi Monica, Scarpa Alice, Selmi Carlo, Silvestri Alessandra, Sironi Marina, Spadoni Ilaria, Spano' Salvatore, Spata Gianmarco, Supino Domenico, Tentorio Paolo, Ummarino Aldo, Valentino Sonia, Voza Antonio, Zaghi Elisa, and Zanon Veronica

Subjects
Metabolome, Microbiota, CHI3L1, COVID-19, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Background and Aims: The SARS-CoV-2 pandemic has overwhelmed the treatment capacity of the health care systems during the highest viral diffusion rate. Patients reaching the emergency department had to be either hospitalized (inpatients) or discharged (outpatients). Still, the decision was taken based on the individual assessment of the actual clinical condition, without specific biomarkers to predict future improvement or deterioration, and discharged patients often returned to the hospital for aggravation of their condition. Here, we have developed a new combined approach of omics to identify factors that could distinguish coronavirus disease 19 (COVID-19) inpatients from outpatients. Methods: Saliva and blood samples were collected over the course of two observational cohort studies. By using machine learning approaches, we compared salivary metabolome of 50 COVID-19 patients with that of 270 healthy individuals having previously been exposed or not to SARS-CoV-2. We then correlated the salivary metabolites that allowed separating COVID-19 inpatients from outpatients with serum biomarkers and salivary microbiota taxa differentially represented in the two groups of patients. Results: We identified nine salivary metabolites that allowed assessing the need of hospitalization. When combined with serum biomarkers, just two salivary metabolites (myo-inositol and 2-pyrrolidineacetic acid) and one serum protein, chitinase 3-like-1 (CHI3L1), were sufficient to separate inpatients from outpatients completely and correlated with modulated microbiota taxa. In particular, we found Corynebacterium 1 to be overrepresented in inpatients, whereas Actinomycetaceae F0332, Candidatus Saccharimonas, and Haemophilus were all underrepresented in the hospitalized population. Conclusion: This is a proof of concept that a combined omic analysis can be used to stratify patients independently from COVID-19.

Published
2022
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3. NaCl enhances CD8+ T cell effector functions in cancer immunotherapy

Author

Scirgolea, Caterina, Sottile, Rosa, De Luca, Marco, Susana, Alberto, Carnevale, Silvia, Puccio, Simone, Ferrari, Valentina, Lise, Veronica, Contarini, Giorgia, Scarpa, Alice, Scamardella, Eloise, Feno, Simona, Camisaschi, Chiara, De Simone, Gabriele, Basso, Gianluca, Giuliano, Desiree, Mazza, Emilia Maria Cristina, Gattinoni, Luca, Roychoudhuri, Rahul, Voulaz, Emanuele, Di Mitri, Diletta, Simonelli, Matteo, Losurdo, Agnese, Pozzi, Davide, Tsui, Carlson, Kallies, Axel, Timo, Sara, Martano, Giuseppe, Barberis, Elettra, Manfredi, Marcello, Rescigno, Maria, Jaillon, Sebastien, and Lugli, Enrico

Published
2024
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4. BTN2A1 targeting reprograms M2-like macrophages and TAMs via SYK and MAPK signaling

Author

Kerneur, Clément, Foucher, Etienne, Guillén Casas, Jaime, Colazet, Magali, Le, Kieu-Suong, Fullana, Marie, Bergot, Elise, Audemard, Corentin, Drapeau, Marion, Louche, Pauline, Gorvel, Laurent, Rouvière, Marie-Sarah, Boucherit, Nicolas, Audebert, Stéphane, Magrini, Elena, Carnevale, Silvia, de Gassart, Aude, Madakamutil, Loui, Mantovani, Alberto, Garlanda, Cecilia, Agaugué, Sophie, Cano, Carla E., and Olive, Daniel

Published
2024
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5. The long Pentraxin PTX3 serves as an early predictive biomarker of co-infections in COVID-19

Author

Accornero, Stefano, Aghemo, Alessio, Ali, Hussam, Angelini, Claudio, Arcari, Ivan, Arosio, Paola, Azzolini, Elena, Baccarin, Alessandra, Badalamenti, Salvatore, Baggio, Sara, Barbagallo, Michela, Barberi, Caterina, Barbic, Franca, Barbieri, Viviana, Barbone, Alessandro, Basciu, Alessio, Bocciolone, Monica, Borea, Federica, Borroni, Mario, Bresciani, Gianluigi, Brunetta, Enrico, Bulletti, Cinzia, Cadonati, Cristina, Calabro', Lorenzo, Calatroni, Marta, Calvetta Albania, Antonietta, Cannata, Francesco, Canziani, Lorenzo, Capretti Giovanni, Luigi, Carlani, Elisa, Carrone, Flaminia, Casana, Maddalena, Cecconi, Maurizio, Ceriotti, Carlo, Ciccarelli, Michele, Cimino, Matteo, Ciuffini, Leonardo, Colaizzi, Chiara, Colapietro, Francesca, Costa, Guido, Cozzi, Ottavia, Craviotto, Vincenzo, Crespi, Chiara, Crippa, Massimo, Da Rio, Leonardo, Dal Farra, Sara, D'Antonio, Federica, De Ambroggi, Guido, De Donato, Massimo, De Lucia, Francesca, De Santis, Maria, Delle Rose, Giacomo, Di Pilla, Marina, Dipaola, Franca, Dipasquale, Andrea, Dipasquale, Angelo, Droandi, Ginevra, Fazio, Roberta, Ferrante, Giuseppe, Ferrara Elisa, Chiara, Ferrari Matteo, Carlo, Ferri, Sebastian, Folci, Marco, Foresti, Sara, Franchi, Eloisa, Fraolini, Elia, Fugazza, Alessandro, Furfaro, Federica, Galimberti, Paola, Galtieri Alessia, Piera, Gavazzi, Francesca, Generali, Elena, Goletti, Benedetta, Guidelli, Giacomo, Jacobs, Flavia, Kurihara, Hayato, Lagioia, Michele, Libre', Luca, Lleo, Ana, Loiacono, Ferdinando, Lughezzani, Giovanni, Maccallini, Marta, Maiorino Alfonso, Francesco, Malesci, Alberto, Mantovani, Riccardo, Marchettini, Davide, Marinello, Arianna, Markopoulos, Nikolaos, Masetti, Chiara, Milani, Angelo, Mirani, Marco, Morelli, Paola, Motta, Francesca, Mundula, Valeria, Nigro, Mattia, Omodei, Paolo, Ormas, Monica, Pagliaro, Arianna, Paliotti, Roberta, Parigi Tommaso, Lorenzo, Pedale, Rosa, Pegoraro, Francesco, Pellegatta, Gaia, Pellegrino, Marta, Petriello, Gennaro, Piccini, Sara, Pocaterra, Daria, Poliani, Laura, Preatoni, Paoletta, Procopio, Fabio, Puggioni, Francesca, Pugliese, Luca, Racca, Francesca, Randazzo, Michele, Regazzoli Lancini, Damiano, Reggiani, Francesco, Rodolfi, Stefano, Ruongo, Lidia, Sacco, Clara, Sandri Maria, Teresa, Savi, Marzia, Scarfo', Iside, Shiffer, Dana, Sicoli, Federico, Solano, Simone, Solitano, Virginia, Stainer, Anna, Stella Matteo, Carlo, Strangio, Giuseppe, Taormina, Antonio, Testoni, Lucia, Tordato, Federica, Trabucco, Angela, Ulian, Luisa, Valentino, Rossella, Valeriano, Chiara, Vena, Walter, Verlingieri, Simona, Vespa, Edoardo, Voza, Antonio, Zanuso, Valentina, Zilli, Alessandra, Anfray, Clement, Belgiovine, Cristina, Bertocchi, Alice, Bombace, Sara, Brescia, Paola, Calcaterra, Francesca, Calvi, Michela, Cancellara, Assunta, Capucetti, Arianna, Carenza, Claudia, Carloni, Sara, Carnevale, Silvia, Cazzetta, Valentina, Coianiz, Nicolò, Darwich, Abbass, Davoudian, Sadaf, De Paoli, Federica, Di Donato, Rachele, Digifico, Elisabeth, Durante, Barbara, Farina Floriana, Maria, Ferrari, Valentina, Fornasa, Giulia, Franzese, Sara, Ghasemi, Somayehsadat, Gil Gomez, Antonio, Giugliano, Silvia, Gomes Ana, Rita, Lizier, Michela, Lo Cascio, Antonino, Melacarne, Alessia, Mozzarelli, Alessandro, My, Ilaria, Oresta, Bianca, Pasqualini, Fabio, Pastò, Anna, Pelamatti, Erica, Perucchini, Chiara, Pozzi, Chiara, Rimoldi, Valeria, Rimoldi, Monica, Scarpa, Alice, Scavello, Francesco, Silvestri, Alessandra, Sironi, Marina, Spadoni, Ilaria, Spano', Salvatore, Spata, Gianmarco, Supino, Domenico, Tentorio, Paolo, Ummarino, Aldo, Valentino, Sonia, Zaghi, Elisa, Zanon, Veronica, Mapelli, Sarah N., Nappi, Emanuele, García Martín, Ian David, Leone, Roberto, Angelotti, Giovanni, Zhong, Hang, Magrini, Elena, Stravalaci, Matteo, Protti, Alessandro, Santini, Alessandro, Costantini, Elena, Savevski, Victor, Bottazzi, Barbara, Bartoletti, Michele, Mantovani, Alberto, and Garlanda, Cecilia

Published
2024
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6. Supplementary Table 2 from Neutrophils Mediate Protection Against Colitis and Carcinogenesis by Controlling Bacterial Invasion and IL22 Production by γδ T Cells

Author

Carnevale, Silvia, primary, Ponzetta, Andrea, primary, Rigatelli, Anna, primary, Carriero, Roberta, primary, Puccio, Simone, primary, Supino, Domenico, primary, Grieco, Giovanna, primary, Molisso, Piera, primary, Di Ceglie, Irene, primary, Scavello, Francesco, primary, Perucchini, Chiara, primary, Pasqualini, Fabio, primary, Recordati, Camilla, primary, Tripodo, Claudio, primary, Belmonte, Beatrice, primary, Mariancini, Andrea, primary, Kunderfranco, Paolo, primary, Sciumè, Giuseppe, primary, Lugli, Enrico, primary, Bonavita, Eduardo, primary, Magrini, Elena, primary, Garlanda, Cecilia, primary, Mantovani, Alberto, primary, and Jaillon, Sebastien, primary

Published
2024
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7. Supplementary Table 1 from Neutrophils Mediate Protection Against Colitis and Carcinogenesis by Controlling Bacterial Invasion and IL22 Production by γδ T Cells

Author

Carnevale, Silvia, primary, Ponzetta, Andrea, primary, Rigatelli, Anna, primary, Carriero, Roberta, primary, Puccio, Simone, primary, Supino, Domenico, primary, Grieco, Giovanna, primary, Molisso, Piera, primary, Di Ceglie, Irene, primary, Scavello, Francesco, primary, Perucchini, Chiara, primary, Pasqualini, Fabio, primary, Recordati, Camilla, primary, Tripodo, Claudio, primary, Belmonte, Beatrice, primary, Mariancini, Andrea, primary, Kunderfranco, Paolo, primary, Sciumè, Giuseppe, primary, Lugli, Enrico, primary, Bonavita, Eduardo, primary, Magrini, Elena, primary, Garlanda, Cecilia, primary, Mantovani, Alberto, primary, and Jaillon, Sebastien, primary

Published
2024
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8. Supplementary Figure S3 from Neutrophils Mediate Protection Against Colitis and Carcinogenesis by Controlling Bacterial Invasion and IL22 Production by γδ T Cells

Author

Carnevale, Silvia, primary, Ponzetta, Andrea, primary, Rigatelli, Anna, primary, Carriero, Roberta, primary, Puccio, Simone, primary, Supino, Domenico, primary, Grieco, Giovanna, primary, Molisso, Piera, primary, Di Ceglie, Irene, primary, Scavello, Francesco, primary, Perucchini, Chiara, primary, Pasqualini, Fabio, primary, Recordati, Camilla, primary, Tripodo, Claudio, primary, Belmonte, Beatrice, primary, Mariancini, Andrea, primary, Kunderfranco, Paolo, primary, Sciumè, Giuseppe, primary, Lugli, Enrico, primary, Bonavita, Eduardo, primary, Magrini, Elena, primary, Garlanda, Cecilia, primary, Mantovani, Alberto, primary, and Jaillon, Sebastien, primary

Published
2024
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9. Data from Neutrophils Mediate Protection Against Colitis and Carcinogenesis by Controlling Bacterial Invasion and IL22 Production by γδ T Cells

Author

Carnevale, Silvia, primary, Ponzetta, Andrea, primary, Rigatelli, Anna, primary, Carriero, Roberta, primary, Puccio, Simone, primary, Supino, Domenico, primary, Grieco, Giovanna, primary, Molisso, Piera, primary, Di Ceglie, Irene, primary, Scavello, Francesco, primary, Perucchini, Chiara, primary, Pasqualini, Fabio, primary, Recordati, Camilla, primary, Tripodo, Claudio, primary, Belmonte, Beatrice, primary, Mariancini, Andrea, primary, Kunderfranco, Paolo, primary, Sciumè, Giuseppe, primary, Lugli, Enrico, primary, Bonavita, Eduardo, primary, Magrini, Elena, primary, Garlanda, Cecilia, primary, Mantovani, Alberto, primary, and Jaillon, Sebastien, primary

Published
2024
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11. Neutrophils mediate protection against colitis and carcinogenesis by controlling bacterial invasion and IL-22 production by γδ T cells

Author

Carnevale, Silvia, primary, Ponzetta, Andrea, additional, Rigatelli, Anna, additional, Carriero, Roberta, additional, Puccio, Simone, additional, Supino, Domenico, additional, Grieco, Giovanna, additional, Molisso, Piera, additional, Di Ceglie, Irene, additional, Scavello, Francesco, additional, Perucchini, Chiara, additional, Pasqualini, Fabio, additional, Recordati, Camilla, additional, Tripodo, Claudio, additional, Belmonte, Beatrice, additional, Mariancini, Andrea, additional, Kunderfranco, Paolo, additional, Sciumè, Giuseppe, additional, Lugli, Enrico, additional, Bonavita, Eduardo, additional, Magrini, Elena, additional, Garlanda, Cecilia, additional, Mantovani, Alberto, additional, and Jaillon, Sebastien, additional

Published
2024
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12. Macrophage expression and prognostic significance of the long pentraxin PTX3 in COVID-19

Author

Brunetta, Enrico, Folci, Marco, Bottazzi, Barbara, De Santis, Maria, Gritti, Giuseppe, Protti, Alessandro, Mapelli, Sarah N., Bonovas, Stefanos, Piovani, Daniele, Leone, Roberto, My, Ilaria, Zanon, Veronica, Spata, Gianmarco, Bacci, Monica, Supino, Domenico, Carnevale, Silvia, Sironi, Marina, Davoudian, Sadaf, Peano, Clelia, Landi, Francesco, Di Marco, Fabiano, Raimondi, Federico, Gianatti, Andrea, Angelini, Claudio, Rambaldi, Alessandro, Garlanda, Cecilia, Ciccarelli, Michele, Cecconi, Maurizio, and Mantovani, Alberto

Published
2021
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13. The long Pentraxin PTX3 serves as an early predictive biomarker of co-infections in COVID-19

Author

Scavello, Francesco, Brunetta, Enrico, Mapelli, Sarah N., Nappi, Emanuele, García Martín, Ian David, Sironi, Marina, Leone, Roberto, Solano, Simone, Angelotti, Giovanni, Supino, Domenico, Carnevale, Silvia, Zhong, Hang, Magrini, Elena, Stravalaci, Matteo, Protti, Alessandro, Santini, Alessandro, Costantini, Elena, Savevski, Victor, Voza, Antonio, Bottazzi, Barbara, Bartoletti, Michele, Cecconi, Maurizio, Mantovani, Alberto, Morelli, Paola, Tordato, Federica, and Garlanda, Cecilia

Published
2024
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15. NaCl enhances CD8+T cell effector functions in cancer immunotherapy

Author

Scirgolea, Caterina, Sottile, Rosa, De Luca, Marco, Susana, Alberto, Carnevale, Silvia, Puccio, Simone, Ferrari, Valentina, Lise, Veronica, Contarini, Giorgia, Scarpa, Alice, Scamardella, Eloise, Feno, Simona, Camisaschi, Chiara, De Simone, Gabriele, Basso, Gianluca, Giuliano, Desiree, Mazza, Emilia Maria Cristina, Gattinoni, Luca, Roychoudhuri, Rahul, Voulaz, Emanuele, Di Mitri, Diletta, Simonelli, Matteo, Losurdo, Agnese, Pozzi, Davide, Tsui, Carlson, Kallies, Axel, Timo, Sara, Martano, Giuseppe, Barberis, Elettra, Manfredi, Marcello, Rescigno, Maria, Jaillon, Sebastien, and Lugli, Enrico

Abstract

CD8+T cells control tumors but inevitably become dysfunctional in the tumor microenvironment. Here, we show that sodium chloride (NaCl) counteracts T cell dysfunction to promote cancer regression. NaCl supplementation during CD8+T cell culture induced effector differentiation, IFN-γ production and cytotoxicity while maintaining the gene networks responsible for stem-like plasticity. Accordingly, adoptive transfer of tumor-specific T cells resulted in superior anti-tumor immunity in a humanized mouse model. In mice, a high-salt diet reduced the growth of experimental tumors in a CD8+T cell-dependent manner by inhibiting terminal differentiation and enhancing the effector potency of CD8+T cells. Mechanistically, NaCl enhanced glutamine consumption, which was critical for transcriptional, epigenetic and functional reprogramming. In humans, CD8+T cells undergoing antigen recognition in tumors and predicting favorable responses to checkpoint blockade immunotherapy resembled those induced by NaCl. Thus, NaCl metabolism is a regulator of CD8+T cell effector function, with potential implications for cancer immunotherapy.

Published
2024
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17. A 'Multiomic' Approach of Saliva Metabolomics, Microbiota, and Serum Biomarkers to Assess the Need of Hospitalization in Coronavirus Disease 2019

Author

Chiara Pozzi, Riccardo Levi, Daniele Braga, Francesco Carli, Abbass Darwich, Ilaria Spadoni, Bianca Oresta, Carola Conca Dioguardi, Clelia Peano, Leonardo Ubaldi, Giovanni Angelotti, Barbara Bottazzi, Cecilia Garlanda, Antonio Desai, Antonio Voza, Elena Azzolini, Maurizio Cecconi, Alberto Mantovani, Giuseppe Penna, Riccardo Barbieri, Letterio S. Politi, Maria Rescigno, Aghemo Alessio, Anfray Clement, Badalamenti Salvatore, Belgiovine Cristina, Bertocchi Alice, Bombace Sara, Brescia Paola, Calcaterra Francesca, Calvi Michela, Cancellara Assunta, Capucetti Arianna, Carenza Claudia, Carloni Sara, Carnevale Silvia, Cazzetta Valentina, Cecconi Maurizio, Ciccarelli Michele, Coianiz Nicolò, Darwich Abbass, Lleo de Nalda Ana, De Paoli Federica, Di Donato Rachele, Digifico Elisabeth, Durante Barbara, FARINA Floriana Maria, Ferrari Valentina, Fornasa Giulia, Franzese Sara, Gil Gomez Antonio, Giugliano Silvia, Gomes Ana Rita, Lizier Michela, Lo Cascio Antonino, Melacarne Alessia, Mozzarelli Alessandro, My Ilaria, Oresta Bianca, Pasqualini Fabio, Pastò Anna, Pelamatti Erica, Perucchini Chiara, Pozzi Chiara, Rimoldi Valeria, Rimoldi Monica, Scarpa Alice, Selmi Carlo, Silvestri Alessandra, Sironi Marina, Spadoni Ilaria, Spano' Salvatore, Spata Gianmarco, Supino Domenico, Tentorio Paolo, Ummarino Aldo, Valentino Sonia, Voza Antonio, Zaghi Elisa, and Zanon Veronica

Subjects
PCA, principal component analysis, SVM, support vector machine, ESI, electrospray ionization, FDR, false discovery rate, Microbiota, IgG, immunoglobulin G, COVID-19, LR, logistic regression, Original Research—Basic, CHI3L1, chitinase 3-like-1, ELISA, enzyme-linked immunosorbent assay, PTX3, pentraxin 3, CI, confidence interval, AUC, area under the curve, RFE, recursive feature elimination, Metabolome, CHI3L1, COVID-19, coronavirus disease 19, DT, decision tree
Abstract

Background and Aims The SARS-CoV-2 pandemic has overwhelmed the treatment capacity of the health care systems during the highest viral diffusion rate. Patients reaching the emergency department had to be either hospitalized (inpatients) or discharged (outpatients). Still, the decision was taken based on the individual assessment of the actual clinical condition, without specific biomarkers to predict future improvement or deterioration, and discharged patients often returned to the hospital for aggravation of their condition. Here, we have developed a new combined approach of omics to identify factors that could distinguish coronavirus disease 19 (COVID-19) inpatients from outpatients. Methods Saliva and blood samples were collected over the course of two observational cohort studies. By using machine learning approaches, we compared salivary metabolome of 50 COVID-19 patients with that of 270 healthy individuals having previously been exposed or not to SARS-CoV-2. We then correlated the salivary metabolites that allowed separating COVID-19 inpatients from outpatients with serum biomarkers and salivary microbiota taxa differentially represented in the two groups of patients. Results We identified nine salivary metabolites that allowed assessing the need of hospitalization. When combined with serum biomarkers, just two salivary metabolites (myo-inositol and 2-pyrrolidineacetic acid) and one serum protein, chitinase 3-like-1 (CHI3L1), were sufficient to separate inpatients from outpatients completely and correlated with modulated microbiota taxa. In particular, we found Corynebacterium 1 to be overrepresented in inpatients, whereas Actinomycetaceae F0332, Candidatus Saccharimonas, and Haemophilus were all underrepresented in the hospitalized population. Conclusion This is a proof of concept that a combined omic analysis can be used to stratify patients independently from COVID-19.

Published
2021

18. Differential expression and regulation of MS4A family members in myeloid cells in physiological and pathological conditions

Author

Silva-Gomes, Rita, primary, Mapelli, Sarah N, additional, Boutet, Marie-Astrid, additional, Mattiola, Irene, additional, Sironi, Marina, additional, Grizzi, Fabio, additional, Colombo, Federico, additional, Supino, Domenico, additional, Carnevale, Silvia, additional, Pasqualini, Fabio, additional, Stravalaci, Matteo, additional, Porte, Rémi, additional, Gianatti, Andrea, additional, Pitzalis, Constantino, additional, Locati, Massimo, additional, Oliveira, Maria José, additional, Bottazzi, Barbara, additional, and Mantovani, Alberto, additional

Published
2021
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19. Differential expression and regulation of MS4A family members in myeloid cells in physiological and pathological conditions.

Author

Silva‐Gomes, Rita, Mapelli, Sarah N., Boutet, Marie‐Astrid, Mattiola, Irene, Sironi, Marina, Grizzi, Fabio, Colombo, Federico, Supino, Domenico, Carnevale, Silvia, Pasqualini, Fabio, Stravalaci, Matteo, Porte, Rémi, Gianatti, Andrea, Pitzalis, Constantino, Locati, Massimo, Oliveira, Maria José, Bottazzi, Barbara, and Mantovani, Alberto

Subjects
MYELOID cells, GENETIC regulation, COVID-19, RHEUMATOID arthritis, PROTEIN analysis
Abstract

The MS4A gene family encodes 18 tetraspanin‐like proteins, most of which with unknown function. MS4A1 (CD20), MS4A2 (FcεRIβ), MS4A3 (HTm4), and MS4A4A play important roles in immunity, whereas expression and function of other members of the family are unknown. The present investigation was designed to obtain an expression fingerprint of MS4A family members, using bioinformatics analysis of public databases, RT‐PCR, and protein analysis when possible. MS4A3, MS4A4A, MS4A4E, MS4A6A, MS4A7, and MS4A14 were expressed by myeloid cells. MS4A6A and MS4A14 were expressed in circulating monocytes and decreased during monocyte‐to‐Mϕ differentiation in parallel with an increase in MS4A4A expression. Analysis of gene expression regulation revealed a strong induction of MS4A4A, MS4A6A, MS4A7, and MS4A4E by glucocorticoid hormones. Consistently with in vitro findings, MS4A4A and MS4A7 were expressed in tissue Mϕs from COVID‐19 and rheumatoid arthritis patients. Interestingly, MS4A3, selectively expressed in myeloid precursors, was found to be a marker of immature circulating neutrophils, a cellular population associated to COVID‐19 severe disease. The results reported here show that members of the MS4A family are differentially expressed and regulated during myelomonocytic differentiation, and call for assessment of their functional role and value as therapeutic targets. [ABSTRACT FROM AUTHOR]

Published
2022
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20. Macrophage expression and prognostic significance of the long pentraxin PTX3 in COVID-19

Author

Brunetta, Enrico, primary, Folci, Marco, additional, Bottazzi, Barbara, additional, De Santis, Maria, additional, Gritti, Giuseppe, additional, Protti, Alessandro, additional, Mapelli, Sarah N., additional, Bonovas, Stefanos, additional, Piovani, Daniele, additional, Leone, Roberto, additional, My, Ilaria, additional, Zanon, Veronica, additional, Spata, Gianmarco, additional, Bacci, Monica, additional, Supino, Domenico, additional, Carnevale, Silvia, additional, Sironi, Marina, additional, Davoudian, Sadaf, additional, Peano, Clelia, additional, Landi, Francesco, additional, Di Marco, Fabiano, additional, Raimondi, Federico, additional, Gianatti, Andrea, additional, Angelini, Claudio, additional, Rambaldi, Alessandro, additional, Garlanda, Cecilia, additional, Ciccarelli, Michele, additional, Cecconi, Maurizio, additional, and Mantovani, Alberto, additional

Published
2020
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22. Impact of RAS mutations on the immune infiltrate of colorectal liver metastases: A preliminary study

Author

Polidoro, Michela Anna, primary, Milana, Flavio, additional, Soldani, Cristiana, additional, Franceschini, Barbara, additional, Anselmo, Achille, additional, Colombo, Federico Simone, additional, Di Tommaso, Luca, additional, Cimino, Matteo, additional, Carnevale, Silvia, additional, Lleo, Ana, additional, Jaillon, Sebastien, additional, Torzilli, Guido, additional, and Donadon, Matteo, additional

Published
2020
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24. Neutrophils Driving Unconventional T Cells Mediate Resistance against Murine Sarcomas and Selected Human Tumors

Author

Ponzetta, Andrea, primary, Carriero, Roberta, additional, Carnevale, Silvia, additional, Barbagallo, Marialuisa, additional, Molgora, Martina, additional, Perucchini, Chiara, additional, Magrini, Elena, additional, Gianni, Francesca, additional, Kunderfranco, Paolo, additional, Polentarutti, Nadia, additional, Pasqualini, Fabio, additional, Di Marco, Sabrina, additional, Supino, Domenico, additional, Peano, Clelia, additional, Cananzi, Ferdinando, additional, Colombo, Piergiuseppe, additional, Pilotti, Silvana, additional, Alomar, Suliman Yousef, additional, Bonavita, Eduardo, additional, Galdiero, Maria Rosaria, additional, Garlanda, Cecilia, additional, Mantovani, Alberto, additional, and Jaillon, Sebastien, additional

Published
2019
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25. p38 MAPK differentially controls NK activating ligands at transcriptional and post-transcriptional level on multiple myeloma cells

Author

Soriani, Alessandra, primary, Borrelli, Cristiana, additional, Ricci, Biancamaria, additional, Molfetta, Rosa, additional, Zingoni, Alessandra, additional, Fionda, Cinzia, additional, Carnevale, Silvia, additional, Abruzzese, Maria Pia, additional, Petrucci, Maria Teresa, additional, Ricciardi, Maria Rosaria, additional, La Regina, Giuseppe, additional, Di Cesare, Erica, additional, Lavia, Patrizia, additional, Silvestri, Romano, additional, Paolini, Rossella, additional, Cippitelli, Marco, additional, and Santoni, Angela, additional

Published
2016
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26. Effectiveness of the cross-compliance Standard 5.2 'buffer strips' on protecting freshwater against diffuse nitrogen pollution

Author

Gumiero, Bruna, primary, Boz, Bruno, additional, Lagomarsino, Alessandra, additional, Bazzoffi, Paolo, additional, Napoli, Rosario, additional, Montemurro, Francesco, additional, Borrelli, Lamberto, additional, Francaviglia, Rosa, additional, Carnevale, Silvia, additional, Rocchini, Andrea, additional, Agnelli, Alessandro Elio, additional, Fiore, Angelo, additional, Cabassi, Giovanni, additional, Pennelli, Bruno, additional, Moretti, Giorgio, additional, Gasparini, Andrea, additional, Pipitone, Giuseppina, additional, and Sansone, Luigi, additional

Published
2016
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27. Environmental effectiveness of GAEC cross-compliance standard 1.1c ‘Maintenance of farm channel networks and field convexity’ and economic evaluation of the competitiveness gap for farmers

Author

Bazzoffi, Paolo, primary, Pellegrini, Sergio, additional, Carnevale, Silvia, additional, Borrelli, Lamberto, additional, Speroni, Marisanna, additional, Furlan, Lorenzo, additional, Chiarini, Francesca, additional, Colauzzi, Michele, additional, Fracasso, Francesco, additional, Fedrizzi, Marco, additional, Guerrieri, Mirko, additional, Pagano, Mauro, additional, Puri, Daniele, additional, and Sperandio, Giulio, additional

Published
2016
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29. Environmental effectiveness of GAEC cross-compliance Standard 3.1 Ploughing in good soil moisture conditions and economic evaluation of the competitiveness gap for farmers

Author

Francaviglia, Rosa, primary, Carroni, Antonio Melchiorre, additional, Ruda, Paola, additional, Salis, Mauro, additional, Bazzoffi, Paolo, additional, Carnevale, Silvia, additional, Rocchini, Andrea, additional, Troccoli, Antonio, additional, Russo, Mario, additional, Speroni, Marisanna, additional, Borrelli, Lamberto, additional, Cabassi, Giovanni, additional, Neri, Ulderico, additional, Napoli, Rosario, additional, Falcucci, Margherita, additional, Pennelli, Bruno, additional, Simonetti, Giampiero, additional, Migliore, Melania, additional, Piccini, Chiara, additional, Ventrella, Domenico, additional, Vonella, Alessandro Vittorio, additional, Giglio, Luisa, additional, Fornaro, Francesco, additional, Castellini, Mirko, additional, Modugno, Francesca, additional, Montemurro, Francesco, additional, Fiore, Angelo, additional, Diacono, Mariangela, additional, Furlan, Lorenzo, additional, Chiarini, Francesca, additional, Colauzzi, Michele, additional, Barbieri, Antonio, additional, Fagotto, Francesco, additional, Fedrizzi, Marco, additional, Fanigliulo, Roberto, additional, Pagano, Mauro, additional, Sperandio, Giulio, additional, Guerrieri, Mirko, additional, and Puri, Daniele, additional

Published
2015
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30. Environmental effectiveness of GAEC cross-compliance standard 2.2 "Maintaining the level of soil organic matter through crop rotation" and economic evaluation of the competitiveness gap for farmers

Author

Borrelli, Lamberto, primary, Farina, Roberta, additional, Bazzoffi, Paolo, additional, Carroni, Antonio Melchiorre, additional, Ruda, Paola, additional, Salis, Mauro, additional, Carnevale, Silvia, additional, Rocchini, Andrea, additional, Virzì, Nino, additional, Intrigliolo, Francesco, additional, Palumbo, Massimo, additional, Cambrea, Michele, additional, Platania, Alfio, additional, Sciacca, Fabiola, additional, Licciardello, Stefania, additional, Troccoli, Antonio, additional, Russo, Mario, additional, Speroni, Marisanna, additional, Cabassi, Giovanni, additional, Degano, Luigi, additional, Fuccella, Roberto, additional, Savi, Francesco, additional, Francaviglia, Rosa, additional, Neri, Ulderico, additional, Falcucci, Margherita, additional, Simonetti, Giampiero, additional, Masetti, Olimpia, additional, Renzi, Gianluca, additional, Ventrella, Domenico, additional, Vonella, Vittorio Alessandro, additional, Giglio, Luisa, additional, Fornaro, Francesco, additional, Leogrande, Rita, additional, Vitti, Carolina, additional, Mastrangelo, Marcello, additional, Montemurro, Francesco, additional, Fiore, Angelo, additional, Diacono, Mariangela, additional, Furlan, Lorenzo, additional, Chiarini, Francesca, additional, Fracasso, Francesco, additional, Sartori, Erica, additional, Barbieri, Antonio, additional, Fagotto, Francesco, additional, Fedrizzi, Marco, additional, Sperandio, Giulio, additional, Pagano, Mauro, additional, Fanigliulo, Roberto, additional, Guerrieri, Mirko, additional, Puri, Daniele, additional, and Colauzzi, Michele, additional

Published
2015
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33. IL-1R8 acts as an immune checkpoint in CD8+T cells

Author

Supino, Domenico, Mariancini, Andrea, Perucchini, Chiara, Carnevale, Silvia, Ponzetta, Andrea, Carriero, Roberta, Colombo, Federico, Magrini, Elena, Di Marco, Sabrina, Rigatelli, Anna, Cordeiro, Luna, Molgora, Martina, Mapelli, Sarah, Donato, Alessia, Tettamanti, Sarah, Biondi, Andrea, Enrico Lugli, Jaillon, Sebastien, Mantovani, Alberto, and Garlanda, Cecilia

34. Expression and regulation of MS4A molecules in myeloid cells

Author

Silva-Gomes, Rita, Mapelli, Sarah N., Boutet, Marie-Astrid, Mattiola, Irene, Sironi, Marina, Grizzi, Fabio, Colombo, Federico, Domenico Supino, Carnevale, Silvia, Pasqualini, Fabio, Stravalaci, Matteo, Porte, Remi, Gianatti, Andrea, Pitzalis, Constantino, Locati, Massimo, Oliveira, Maria Jose, Bottazzi, Barbara, and Mantovani, Alberto

36. p38 MAPK differentially controls NK activating ligands at transcriptional and post-transcriptional level on multiple myeloma cells.

Author

Soriani, Alessandra, Borrelli, Cristiana, Ricci, Biancamaria, Molfetta, Rosa, Zingoni, Alessandra, Fionda, Cinzia, Carnevale, Silvia, Abruzzese, Maria Pia, Petrucci, Maria Teresa, Ricciardi, Maria Rosaria, La Regina, Giuseppe, Di Cesare, Erica, Lavia, Patrizia, Silvestri, Romano, Paolini, Rossella, Cippitelli, Marco, and Santoni, Angela

Subjects
MULTIPLE myeloma treatment, KILLER cells, MESSENGER RNA
Abstract

The mechanisms that regulate the expression of the NKG2D and DNAM-1 activating ligands are only partially known, but it is now widely established that their expression is finely regulated at transcriptional, post-transcriptional and post-translational level, and involve numerous stress pathways depending on the type of ligand, stressor, and cell context. We show that treatment of Multiple Myeloma (MM) cells with sub-lethal doses of Vincristine (VCR), an anticancer drug that inhibits the assembly of microtubules, stimulates the expression of NKG2D and DNAM-1 activating ligands, rendering these cells more susceptible to NK cell-mediated killing. Herein, we focused our attention on the identification of the signaling pathways leading tode novosurface expression of ULBP-1, and to MICA and PVR upregulation on VCR-treated MM cells, both at protein and mRNA levels. We found that p38MAPK differentially regulates drug-dependent ligand upregulation at transcriptional and post-transcriptional level. More specifically, we observed that ULBP-1 expression is attributable to both increased transcriptional activity mediated by ATM-dependent p53 activation, and enhanced mRNA stability; while the p38-activated E2F1 transcription factor regulates MICA and PVR mRNA expression. All together, our findings reveal a previously unrecognized activity of VCR as anticancer agent, and indicate that in addition to its established ability to arrest cell growth, VCR can also modulate the expression of NKG2D and DNAM-1 activating ligand on tumor cells and thus promoting NK cell-mediated immunosurveillance. [ABSTRACT FROM AUTHOR]

Published
2017
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37. Stromal and Immune Cell Dynamics in Tumor Associated Tertiary Lymphoid Structures and Anti-Tumor Immune Responses

Author

Alessandra Rossi, Beatrice Belmonte, Silvia Carnevale, Antonietta Liotti, Veronica De Rosa, Sebastien Jaillon, Silvia Piconese, Claudio Tripodo, Rossi, Alessandra, Belmonte, Beatrice, Carnevale, Silvia, Liotti, Antonietta, De Rosa, Veronica, Jaillon, Sebastien, Piconese, Silvia, and Tripodo, Claudio

Subjects
Treg, neutrophils, TLS, tumor stroma, Tfh, Cell Biology, Settore MED/08 - Anatomia Patologica, Developmental Biology
Abstract

Tertiary lymphoid structures (TLS) are ectopic lymphoid organs that have been observed in chronic inflammatory conditions including cancer, where they are thought to exert a positive effect on prognosis. Both immune and non-immune cells participate in the genesis of TLS by establishing complex cross-talks requiring both soluble factors and cell-to-cell contact. Several immune cell types, including T follicular helper cells (Tfh), regulatory T cells (Tregs), and myeloid cells, may accumulate in TLS, possibly promoting or inhibiting their development. In this manuscript, we propose to review the available evidence regarding specific aspects of the TLS formation in solid cancers, including 1) the role of stromal cell composition and architecture in the recruitment of specific immune subpopulations and the formation of immune cell aggregates; 2) the contribution of the myeloid compartment (macrophages and neutrophils) to the development of antibody responses and the TLS formation; 3) the immunological and metabolic mechanisms dictating recruitment, expansion and plasticity of Tregs into T follicular regulatory cells, which are potentially sensitive to immunotherapeutic strategies directed to costimulatory receptors or checkpoint molecules.

Published
2022
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38. Neutrophils Mediate Protection Against Colitis and Carcinogenesis by Controlling Bacterial Invasion and IL22 Production by γδ T Cells.

Author

Carnevale S, Ponzetta A, Rigatelli A, Carriero R, Puccio S, Supino D, Grieco G, Molisso P, Di Ceglie I, Scavello F, Perucchini C, Pasqualini F, Recordati C, Tripodo C, Belmonte B, Mariancini A, Kunderfranco P, Sciumè G, Lugli E, Bonavita E, Magrini E, Garlanda C, Mantovani A, and Jaillon S

Subjects
Animals, Humans, Mice, Carcinogenesis, Colitis pathology, Disease Models, Animal, Mice, Inbred C57BL, Mice, Knockout, Colitis, Ulcerative metabolism, Colitis-Associated Neoplasms pathology, Neutrophils immunology, Neutrophils metabolism
Abstract

Neutrophils are the most abundant leukocytes in human blood and play a primary role in resistance against invading microorganisms and in the acute inflammatory response. However, their role in colitis and colitis-associated colorectal cancer is still under debate. This study aims to dissect the role of neutrophils in these pathologic contexts by using a rigorous genetic approach. Neutrophil-deficient mice (Csf3r-/- mice) were used in classic models of colitis and colitis-associated colorectal cancer and the role of neutrophils was assessed by histologic, cellular, and molecular analyses coupled with adoptive cell transfer. We also performed correlative analyses using human datasets. Csf3r-/- mice showed increased susceptibility to colitis and colitis-associated colorectal cancer compared with control Csf3r+/+ mice and adoptive transfer of neutrophils in Csf3r-/- mice reverted the phenotype. In colitis, Csf3r-/- mice showed increased bacterial invasion and a reduced number of healing ulcers in the colon, indicating a compromised regenerative capacity of epithelial cells. Neutrophils were essential for γδ T-cell polarization and IL22 production. In patients with ulcerative colitis, expression of CSF3R was positively correlated with IL22 and IL23 expression. Moreover, gene signatures associated with epithelial-cell development, proliferation, and antimicrobial response were enriched in CSF3Rhigh patients. Our data support a model where neutrophils mediate protection against intestinal inflammation and colitis-associated colorectal cancer by controlling the intestinal microbiota and driving the activation of an IL22-dependent tissue repair pathway., (©2024 The Authors; Published by the American Association for Cancer Research.)

Published
2024
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