TIGIT disruption rescues the antitumor activity of low avidity TCR-engineered T cells by increasing TCR signal strength Martina Spiga, Alessia Potenza, Zulma Magnani, Stefano Beretta, Barbara Camisa, Laura Conte, Alessia Airaghi, Neda Mohammadi, Laura Perani, Claudio Doglioni, Maurilio Ponzoni, Francesca Sanvito, Chiara Balestrieri, Lucia Sergi Sergi, Oronza A. Botrugno, Giulio Giovannoni, Giovanni Tonon, Danilo Abbati, Chiara Iozzi, Maximilian Reichert, Hana Algul, Arianna Pocaterra, Martina Fiumara, Samuele Ferrari, Alessia Ugolini, Alice Grometto, Giulia Di Lullo, Giovanni Sitia, Giulio Belfiori, Maria Pia Protti, Renato Ostuni, Anna Mondino, Michele Reni, Stefano Crippa, Massimo Falconi, Luigi Naldini, Eliana Ruggiero, Chiara Bonini Nature Communications, 2026 T-cell avidity is a major determinant of Adoptive T cell therapy (ACT) efficacy for cancer treatment. However, high-avidity tumor-specific T cells can rarely be isolated from cancer patients, highlighting the need for strategies to enhance the cytotoxic capacity of low-avidity cells. Here, we rescue the anti-tumor functions of low-avidity T cells against pancreatic ductal adenocarcinoma (PDAC) by knocking-out TIGIT, a key inhibitory molecule expressed on exhausted CD8+ T cells infiltrating gastrointestinal tumors. We uncover that TIGIT disruption by base editing boosts the intracellular signal transduction derived from a weak T cell receptor (TCR) engagement enforcing cytoskeletal rearrangements, thus increasing T cell avidity and stabilizing the immunological synapse. Accordingly, TIGIT disruption enables low-avidity T cells to exert robust degranulation, comparable to that of high-avidity T cells, and potent and durable anti-tumor capacity in vivo in male mice. These results highlight TIGIT knockout as a potential strategy to enhance low-avidity T cell function and broaden the repertoire of TCR engineered T cells in the treatment of pancreatic cancer and other solid malignancies. Anti-tumor functions of low-avidity T cells are often suboptimal. Here the authors show that genetic disruption of TIGIT in TCR-engineered T cells enhances their anti-tumor activity against pancreatic and other gastrointestinal cancers by increasing TCR signal strength.
The genetic basis of the immune response to SARS-CoV-2 infection and vaccination in the Italian municipality of Vo’ Ettore Zapparoli, Enrico Lavezzo, Hélène Tonnelé, Fabio Simeoni, Jing Guo, Klaudia Walter, Anna Sofia Tascini, Sodbo Sharapov, Rebecca Elyanow, Martina Bado, Giorgia Mazzotti, Dmitry Penkov, Marco J. Morelli, Dejan Lazarevic, Nicola Pirastu, Nicole Soranzo, Ilan R. Kirsch, Andrea Crisanti, Stefano Toppo, Paolo Provero, Giovanni Tonon Frontiers in Immunology, 2026 Introduction It is becoming increasingly evident that SARS-CoV-2 infection is here to stay. Therefore, understanding whether genetic variants may impact the response to the virus or vaccination is crucial. Studies on the genetic determinants of immune responses to SARS-CoV-2 have been limited by the scarcity of genetically homogenous populations and longitudinal designs that assess responses to both infection and vaccination in relation to individual genetic variation. Methods Here we performed genotyping and whole-genome sequencing in a well-annotated and intensively followed population from the municipality of Vo’, which has previously provided critical insights into SARS-CoV-2 transmission, infection dynamics and COVID-19 clinical manifestations. Results We identified 99 variants within the major histocompatibility complex (MHC) associated with altered T cell response dynamics following infection. These variants clustered into two semi-independent linkage disequilibrium (LD) blocks, respectively tagged by the HLA-A*01:01 allele and by SNP rs1611581. Additionally, when examining the response to vaccination, we identified 617 MHC genetic variants clustering into 27 semi-independent LD blocks that correlated with either increased or decreased TCR responses. We constructed a polygenic risk score (PRS) that comprehensively captures this genetic variation. Finally, structural modelling of selected variants affecting HLA proteins identified specific amino acid residuals most likely to influence interactions with SARS-CoV-2 epitopes, including arginine at position 114, isoleucine at position 97, and alanine at position 152 of the HLA-A molecule. Conclusion Together, these findings provide robust evidence that genetic profiles modulate the immune response to SARS-CoV-2 in a longitudinal setting, offering insights that may inform further public health interventions.
Early tolerance and late persistence as alternative drug responses in cancer Simona Punzi, Davide Cittaro, Guido Gatti, Gemma Crupi, Oronza A. Botrugno, Antonino Alex Cartalemi, Alon Gutfreund, Caterina Oneto, Valentina Giansanti, Chiara Battistini, Giovanni Santacatterina, Lucrezia Patruno, Ilaria Villanti, Martina Palumbo, Daniel J. Laverty, Francesca Giannese, Alex Graudenzi, Giulio Caravagna, Marco Antoniotti, Zachary Nagel, Ugo Cavallaro, Luisa Lanfrancone, Timothy A. Yap, Giulio Draetta, Nathalie Balaban, Giovanni Tonon Nature Communications, 2025 Bacteria withstand antibiotic treatment through three alternative mechanisms: resistance, persistence or tolerance. While resistance and persistence have been described, whether drug-induced tolerance exists in cancer cells remains largely unknown. Here, we show that human cancer cells elicit a tolerant response when exposed to commonly used chemotherapy regimens, propelled by the pervasive activation of autophagy, leading to the comprehensive activation of DNA damage repair pathways. After prolonged drug exposure, such tolerant responses morph into persistence, whereby the increased DNA damage repair is entirely reversed. The central regulator of mitophagy PINK1 drives this reduction in DNA repair via the cytoplasmic relocalization of the cell identity master HNF4A, thus hampering HNF4A transcriptional activation of DNA repair genes. We conclude that exposing cancer cells to relevant standard-of-care antitumour therapies induces a pervasive drug-induced tolerant response that might be broadly exploited to increase the impact of first-line, adjuvant treatments and debulking in advanced cancers. Bacteria are able to withstand antibiotic treatment through three mechanisms, resistance, persistence or tolerance. Here, the authors investigate whether such mechanisms as defined in bacteria also apply to human cancer cells, finding that exposure to chemotherapy elicits an atavistic tolerant response in human cancer cells, providing key survival advantages.
The italian national genomic strategy: current status, challenges, and future perspectives in clinical practice and public health Francesco Andrea Causio, Sara Farina, Alessandra Maio, Flavia Beccia, Luigi Russo, Valentina Baccolini, Matteo Chiara, Americo Cicchetti, Gualtiero I. Colombo, Giovanni Comandé, Domenico Coviello, Ruggero De Maria, Massimo Delledonne, Corrado De Vito, Daniela Galeone, Paolo Gasparini, David Horner, Giovanni Martinelli, Carolina Marzuillo, Laura Palazzani, Erica Pitini, Maurizio Sanguinetti, Aldo Scarpa, Marco Tartaglia, Francesco Danilo Tiziano, Giovanni Tonon, Bruno Dallapiccola, Paolo Villari, Giovanna Elisa Calabrò, Stefania Boccia Journal of Community Genetics, 2025 This article presents the outcomes of a national initiative aimed at developing a technical document to support the future Italian National Genomic Strategy, carried out from 2021 to 2024 through the collaboration of 14 research institutions. The project was designed to align with major European genomic initiatives, particularly the “1 + Million Genomes” (1 + MG) Declaration and its supporting programs, including Beyond 1 Million Genomes (B1 + MG), the Genomic Data Infrastructure (GDI), and Genome of Europe (GoE). The initiative was structured around 12 National Mirror Groups (NMGs), each addressing a specific domain such as clinical implementation, ethical and legal issues, data governance, health economics, and public engagement. Through expert consensus and coordinated activities, the project produced a comprehensive technical document outlining seven strategic lines and related intervention areas. These include the integration of genomic testing into clinical practice, development of specialized genomic centers, creation of a national genomic data infrastructure, professional training, and public education. The proposed strategy emphasizes equitable access to genomic medicine, the use of health technology assessment to evaluate new technologies, and the importance of citizen engagement and literacy. By fostering collaboration among institutions, healthcare professionals, and the public, the final goal is to position Italy as a leader in genomic medicine and ensure the responsible, effective, and ethical use of genomics in public health and clinical care.
Imprints of somatic hypermutation on B-cell receptor immunoglobulins post-infection versus post-vaccination against SARS-CoV-2 Elisavet Vlachonikola, Nikolaos Pechlivanis, Georgios Karakatsoulis, Massimo Degano, Fotis Psomopoulos, Andrea Crisanti, Giovanni Tonon, Paolo Ghia, Kostas Stamatopoulos, Enrico Lavezzo, Anastasia Chatzidimitriou Immunohorizons, 2025 Published evidence supports significant heterogeneity of immune responses among individuals infected with or vaccinated against SARS-CoV-2. This highlights the need for in-depth investigation of the implicated processes toward refined understanding and improved management of COVID-19. The main objective of the present study was to investigate the dynamics of B cell responses to SARS-CoV-2, focusing on how initial infection and subsequent vaccination influence the immunoglobulin gene repertoire, with special emphasis on the impact of somatic hypermutation (SHM) on antibody maturation. Samples were collected from 81 individuals infected by SARS-CoV-2 in the municipality of Vo' during the first pandemic wave in 2020. For 25 of them, sampling was repeated 7 d after completing the primary vaccination series. Deep immunogenetic analysis of the B-cell receptor immunoglobulin (BcR IG) gene repertoire was performed using targeted next-generation sequencing. Bioinformatics analysis focused on repertoire metrics, prediction of IG antigen specificity, and detailed profiling of the SHM patterns. Significant expansions of unmutated sequences early post-infection suggest extrafollicular B cell maturation. In contrast, vaccination promoted SHM acquisition, indicating a germinal center–dependent response, and pronounced repertoire renewal. Restricted SHMs in SARS-homologous clonotypes along with preferential targeting of specific codons within the VH domain post-vaccination support ongoing affinity maturation within germinal centers. Differences in the BcR IG profiles post-infection versus post-vaccination allude to distinct trajectories in B cell maturation. Distinct profiles of SHM targeting reflect ongoing affinity maturation post-vaccination, with implications for optimizing preventive and therapeutic interventions against COVID-19.
Systemic delivery of cadherin 17–specific CAR T cells allows effective and safe targeting of colorectal cancer liver metastases Beatrice Greco, Rita El Khoury, Chiara Balestrieri, Camilla Sirini, Alice Machado, Federica De Girardi, Laura De Rossi, Oronza Antonietta Botrugno, Giulio Giovannoni, Laura Falcone, Barbara Camisa, Elena Tiziano, Katia Palmisano, Edoardo Campodonico, Marta Angiola Moresco, Laura Perani, Alice Bergamini, Amanda Facoetti, Federica Ungaro, Giovanni Tonon, Emmanuel Donnadieu, Claudio Doglioni, Fabio Ciceri, Chiara Bonini, Monica Casucci Science Translational Medicine, 2025 Liver metastases represent the leading cause of death in patients with colorectal cancer (CRC). Chimeric antigen receptor (CAR) T cell therapy holds promise in this context, but any effort to bring it to the bedside requires careful antigen selection and testing in clinically relevant models. Here, we identified cadherin-17 (CDH17) as a candidate antigen for CAR T cell therapy of CRC liver metastases. We hence designed human CDH17 CARs differing in antigen binding and extracellular spacer regions and compared the different constructs in preclinical models of antitumor efficacy, cytokine release syndrome, and on-target off-tumor toxicity. Whereas the binding domains differed in efficacy in vitro, the spacer region shaped the kinetics of the CAR T cells in vivo. When used in a CRC liver xenograft model, CDH17 CAR T cells efficiently suppressed tumor growth upon either systemic or locoregional administration. However, when tested in mice reconstituted with a human immune system, CAR T cells injected locally caused a particularly harsh cytokine release syndrome. Confocal microscopy revealed that CDH17 is exposed on the entire surface of tumor cells, whereas its expression in healthy colon is restricted to lateral junctions between epithelial cells. Accordingly, CDH17 CAR T cells showed dose-dependent cytokine release in response to CRC tissue slices while displaying no reaction against healthy colon tissue samples. Overall, these findings support systemic delivery of CDH17 CAR T cells as a safe and effective approach to treat CRC liver metastases and pave the way for a phase 1/2 clinical trial.
Leveraging the potential of 1.0-mm i.d. columns in UHPLC-HRMS-based untargeted metabolomics Danila La Gioia, Emanuela Salviati, Manuela Giovanna Basilicata, Claudia Felici, Oronza A. Botrugno, Giovanni Tonon, Eduardo Sommella, Pietro Campiglia Analytical and Bioanalytical Chemistry, 2025 Untargeted metabolomics UHPLC-HRMS workflows typically employ narrowbore 2.1-mm inner diameter (i.d.) columns. However, the wide concentration range of the metabolome and the need to often analyze small sample amounts poses challenges to these approaches. Reducing the column diameter could be a potential solution. Herein, we evaluated the performance of a microbore 1.0-mm i.d. setup compared to the 2.1-mm i.d. benchmark for untargeted metabolomics. The 1.0-mm i.d. setup was implemented on a micro-UHPLC system, while the 2.1-mm i.d. on a standard UHPLC, both coupled to quadrupole-orbitrap HRMS. On polar standard metabolites, a sensitivity gain with an average 3.8-fold increase over the 2.1-mm i.d., along with lower LOD (LODavg 1.48 ng/mL vs. 6.18 ng/mL) and LOQ (LOQavg 4.94 ng/mL vs. 20.60 ng/mL), was observed. The microbore method detected and quantified all metabolites at LLOQ with respect to 2.1, also demonstrating good repeatability with lower CV% for retention times (0.29% vs. 0.63%) and peak areas (4.65% vs. 7.27%). The analysis of various samples, in both RP and HILIC modes, including different plasma volumes, dried blood spots (DBS), and colorectal cancer (CRC) patient-derived organoids (PDOs), in full scan-data dependent mode (FS-DDA) reported a significant increase in MS1 and MS2 features, as well as MS/MS spectral matches by 38.95%, 39.26%, and 18.23%, respectively. These findings demonstrate that 1.0-mm i.d. columns in UHPLC-HRMS could be a potential strategy to enhance coverage for low-amount samples while maintaining the same analytical throughput and robustness of 2.1-mm i.d. formats, with reduced solvent consumption.
Evolutionary fingerprints of epithelial-to-mesenchymal transition Luigi Perelli, Li Zhang, Sarah Mangiameli, Francesca Giannese, Krishnan K. Mahadevan, Fuduan Peng, Francesca Citron, Hania Khan, Courtney Le, Enrico Gurreri, Federica Carbone, Andrew J. C. Russell, Melinda Soeung, Truong Nguyen Anh Lam, Sebastian Lundgren, Sujay Marisetty, Cihui Zhu, Desiree Catania, Alaa M. T. Mohamed, Ningping Feng, Jithesh Jose Augustine, Alessandro Sgambato, Giampaolo Tortora, Giulio F. Draetta, Giovanni Tonon, Andrew Futreal, Virginia Giuliani, Alessandro Carugo, Andrea Viale, Michael P. Kim, Timothy P. Heffernan, Linghua Wang, Raghu Kalluri, Davide Cittaro, Fei Chen, Giannicola Genovese Nature, 2025
DNA methylation alterations in prostate cancer: from diagnosis to treatment Francesco Barletta, Marco Bandini, Giuseppe Ottone Cirulli, Paolo Zaurito, Roberta Lucianò, Francesca Giannese, Giulia Maria Scotti, Caterina Oneto, Nazario Tenace, Federico Scarfò, Marco J. Morelli, Dejan Lazarevic, Francesco De Cobelli, Maurilio Ponzoni, Claudio Doglioni, Giovanni Tonon, Giorgio Gandaglia, Francesco Montorsi, Alberto Briganti Translational Andrology and Urology, 2025 Epigenetics, particularly DNA methylation, plays a crucial role in gene activation and deactivation. Indeed, modification of this pathway has been well described as promoter of cancer development in many settings. Hypermethylation of CpG islands has also been described as a significant epigenetic alteration in prostate cancer (PCa), being associated with gene silencing and tumour progression. Key studies have shown that specific genes, such as GSTP1, APC, and RARb2, exhibit significant epigenetic alterations in PCa, with their methylation profiles showing potential utility as biomarkers in the diagnostic setting. Furthermore, comprehensive methylation analyses have identified numerous differentially methylated CpGs and relative molecular pathways associated with PCa carcinogenesis and progression, thus enhancing the understanding of its molecular underpinnings. Finally, therapies targeting DNA methylation, such as DNA methyltransferases (DNMTs) inhibitors, show potential in overcoming drug resistance in advanced PCa treatment. Consequently, dissecting epigenetic mechanisms, and in particular DNA methylation, is fundamental for understanding PCa carcinogenesis, providing valuable insights for clinical decisions and development of targeted therapies. Given the above premises, this review aims to provide an overview of the role of DNA methylation aberrations in PCa, highlighting current and future directions for exploring the epigenetic landscape to better understand the origins and progression of this disease.
Microfluidics for 3D dynamic cell cultures in 384 multiwell format Convegno Nazionale Di Bioingegneria, 2025
Cancer Organoids as reliable disease models to drive clinical development of novel therapies Giovanni Blandino, Ronit Satchi-Fainaro, Ingeborg Tinhofer, Giovanni Tonon, Sarah C. Heilshorn, Yong-Jun Kwon, Ana Pestana, Carlotta Frascolla, Luca Pompili, Aurora Puce, Sara Iachettini, Annalisa Tocci, Sofia Karkampouna, Marianna Kruithof-de Julio, Piera Tocci, Nicla Porciello, Klizia Maccaroni, Daniela Rutigliano, Xiling Shen, Gennaro Ciliberto Journal of Experimental and Clinical Cancer Research, 2024
Erratum: Developing PRISM: A Pragmatic Institutional Survey and Bench Marking Tool to Measure Digital Research Maturity of Cancer Centers Carlos Berenguer Albiñana, Matteo Pallocca, Hayley Fenton, Will Sopwith, Charlie Van Eden, Olof Akre, Annika Auranen, François Bocquet, Marina Borges, Emiliano Calvo, John Corkett, Serena Di Cosimo, Nicola Gentili, Julien Guérin, Sissel Jor, Tomas Kazda, Alenka Kolar, Tim Kuschel, Maria Julia Lostes, Chiara Paratore, Paolo Pedrazzoli, Marko Petrovic, Jarno Raid, Miriam Roche, Christoph Schatz, Joelle Thonnard, Giovanni Tonon, Alberto Traverso, Andrea Wolf, Ahmed H. Zedan, Piers Mahon Applied Clinical Informatics, 2024
KDM6A regulates immune response genes in multiple myeloma Daphne Dupere-Richer, Alberto Riva, Benjamin G Barwick, Sayantan Maji, Heidi Casellas Roman, Jianping Li, Umasankar De, Amin Sobh, Gabrielle Quickstad, Crissandra Piper, Marta Kulis, Teresa Ezponda, José-Ignacio Ignacio Martín-Subero, Giovanni Tonon, Weizhou Zhang, Constantine S. Mitsiades, Lawrence H Boise, Richard L Bennett, Jonathan D Licht Blood, 2024
Developing PRISM: A Pragmatic Institutional Survey and Bench Marking Tool to Measure Digital Research Maturity of Cancer Centers Carlos Berenguer Albiñana, Matteo Pallocca, Hayley Fenton, Will Sopwith, Charlie Van Eden, Olof Akre, Annika Auranen, François Bocquet, Marina Borges, Emiliano Calvo, John Corkett, Serena Di Cosimo, Nicola Gentili, Julien Guérin, Sissel Jor, Tomas Kazda, Alenka Kolar, Tim Kuschel, Maria Julia Lostes, Chiara Paratore, Paolo Pedrazzoli, Marko Petrovic, Jarno Raid, Miriam Roche, Christoph Schatz, Joelle Thonnard, Giovanni Tonon, Alberto Traverso, Andrea Wolf, Ahmed H. Zedan, Piers Mahon Applied Clinical Informatics, 2024
The 1+Million Genomes Minimal Dataset for Cancer Michela Riba, Cinzia Sala, Aedin C. Culhane, Åsmund Flobak, Attila Patocs, Kjetil Boye, Karla Plevova, Šárka Pospíšilová, Giorgia Gandolfi, Marco J. Morelli, Gabriele Bucci, Anders Edsjö, Ulrik Lassen, Fátima Al-Shahrour, Nuria Lopez-Bigas, Randi Hovland, Edwin Cuppen, Alfonso Valencia, Helene A. Poirel, Richard Rosenquist, Serena Scollen, Juan Arenas Marquez, Jeroen Belien, Arcangela De Nicolo, Ruggero De Maria, David Torrents, Giovanni Tonon Nature Genetics, 2024
A federated learning system for precision oncology in Europe: DigiONE Piers Mahon, Ismini Chatzitheofilou, Andre Dekker, Xosé Fernández, Geoff Hall, Aslaug Helland, Alberto Traverso, Cedric Van Marcke, Janne Vehreschild, Gennaro Ciliberto, Giovanni Tonon Nature Medicine, 2024
UNCAN.eu: Toward a European Federated Cancer Research Data Hub Michael Boutros, Michael Baumann, Anna Bigas, Linda Chaabane, Julien Guérin, Jens K. Habermann, Aurélien Jobard, Pier Giuseppe Pelicci, Oliver Stegle, Giovanni Tonon, Alfonso Valencia, Eva C. Winkler, Patricia Blanc, Ruggero De Maria, Rene H. Medema, Peter Nagy, Josep Tabernero, Eric Solary Cancer Discovery, 2024
Cancer Evolution: A Multifaceted Affair Giovanni Ciriello, Luca Magnani, Sarah J. Aitken, Leila Akkari, Sam Behjati, Douglas Hanahan, Dan A. Landau, Nuria Lopez-Bigas, Darío G. Lupiáñez, Jean-Christophe Marine, Ana Martin-Villalba, Gioacchino Natoli, Anna C. Obenauf, Elisa Oricchio, Paola Scaffidi, Andrea Sottoriva, Alexander Swarbrick, Giovanni Tonon, Sakari Vanharanta, Johannes Zuber Cancer Discovery, 2024
Germline testing and genetic counseling in biliary tract cancer: an operative proposal to improve the state of art Margherita Rimini, Silvia Presi, Giovanni Battista Pipitone, Annalisa Russo Raucci, Francesca Ratti, Angelo Della Corte, Federica Pedica, Giuseppe Vanella, Giovanni Tonon, Valentina Burgio, Francesco Vitiello, Federico Rossari, Elisabeth Amadeo, Cangi Maria Giulia, Lorenza Pecciarini, Paolo Giorgio Arcidiacono, Francesca Falcinelli, Stefano Cascinu, Francesco De Cobelli, Luca Aldrighetti, Maria Grazia Patricelli, Paola Carrera, Andrea Casadei-Gardini Expert Review of Gastroenterology and Hepatology, 2024
In vivo macrophage engineering reshapes the tumor microenvironment leading to eradication of liver metastases Thomas Kerzel, Giovanna Giacca, Stefano Beretta, Chiara Bresesti, Marco Notaro, Giulia Maria Scotti, Chiara Balestrieri, Tamara Canu, Miriam Redegalli, Federica Pedica, Marco Genua, Renato Ostuni, Anna Kajaste-Rudnitski, Masanobu Oshima, Giovanni Tonon, Ivan Merelli, Luca Aldrighetti, Paolo Dellabona, Nadia Coltella, Claudio Doglioni, Paola M.V. Rancoita, Francesca Sanvito, Luigi Naldini, Mario Leonardo Squadrito Cancer Cell, 2023
Revealing and harnessing CD39 for the treatment of colorectal cancer and liver metastases by engineered T cells Alessia Potenza, Chiara Balestrieri, Martina Spiga, Luca Albarello, Federica Pedica, Francesco Manfredi, Beatrice Claudia Cianciotti, Claudia De Lalla, Oronza A Botrugno, Cristina Faccani, Lorena Stasi, Elena Tassi, Silvia Bonfiglio, Giulia Maria Scotti, Miriam Redegalli, Donatella Biancolini, Barbara Camisa, Elena Tiziano, Camilla Sirini, Monica Casucci, Chiara Iozzi, Danilo Abbati, Fabio Simeoni, Dejan Lazarevic, Ugo Elmore, Guido Fiorentini, Giulia Di Lullo, Giulia Casorati, Claudio Doglioni, Giovanni Tonon, Paolo Dellabona, Riccardo Rosati, Luca Aldrighetti, Eliana Ruggiero, Chiara Bonini Gut, 2023
Preexisting Immunity Drives the Response to Neoadjuvant Chemotherapy in Esophageal Adenocarcinoma Giuseppina Arbore, Luca Albarello, Gabriele Bucci, Marco Punta, Andrea Cossu, Lorella Fanti, Aurora Maurizio, Francesco Di Mauro, Vito Bilello, Gianluigi Arrigoni, Silvia Bonfiglio, Donatella Biancolini, Francesco Puccetti, Ugo Elmore, Luca Vago, Stefano Cascinu, Giovanni Tonon, Riccardo Rosati, Giulia Casorati, Paolo Dellabona Cancer Research, 2023
Neutralising reactivity against SARS-CoV-2 Delta and Omicron variants by vaccination and infection history Enrico Lavezzo, Monia Pacenti, Laura Manuto, Caterina Boldrin, Margherita Cattai, Marco Grazioli, Federico Bianca, Margherita Sartori, Federico Caldart, Gioele Castelli, Michele Nicoletti, Eleonora Nieddu, Elisa Salvadoretti, Beatrice Labella, Ludovico Fava, Maria Cristina Vanuzzo, Vittoria Lisi, Maria Antonello, Carmela Ileana Grimaldi, Chiara Zulian, Claudia Del Vecchio, Mario Plebani, Andrea Padoan, Daniela Maria Cirillo, Alessandra R. Brazzale, Giovanni Tonon, Stefano Toppo, Ilaria Dorigatti, Andrea Crisanti Genome Medicine, 2022
Phylogeography and genomic epidemiology of SARS-CoV-2 in Italy and Europe with newly characterized Italian genomes between February-June 2020 Alessia Lai, Annalisa Bergna, Stefano Toppo, Marina Morganti, Stefano Menzo, Valeria Ghisetti, Bianca Bruzzone, Mauro Codeluppi, Vito Fiore, Emmanuele Venanzi Rullo, Guido Antonelli, Loredana Sarmati, Gaetano Brindicci, Annapaola Callegaro, Caterina Sagnelli, Daniela Francisci, Ilaria Vicenti, Arianna Miola, Giovanni Tonon, Daniela Cirillo, Ilaria Menozzi, Sara Caucci, Francesco Cerutti, Andrea Orsi, Roberta Schiavo, Sergio Babudieri, Giuseppe Nunnari, Claudio M. Mastroianni, Massimo Andreoni, Laura Monno, Davide Guarneri, Nicola Coppola, Andrea Crisanti, Massimo Galli, Gianguglielmo Zehender, Claudia Balotta, Carla della Ventura, Marco Schiuma, Enrico Lavezzo, Paolo Fontana, Luca Bianco, Luigi Bertolotti, Laura Manuto, Marco Grazioli, Federico Bianca, Claudia Del Vecchio, Elisa Franchin, Francesco Onelia, Andrea Spitaleri, Francesca Saluzzo, Giovanni Lorenzin, Stefano Pongolini, Erika Scaltriti, Laura Soliani, Patrizia Bagnarelli, Chiara Turchi, Valerio Onofri, Filomena Melchionda, Adriano Tagliabracci, Elisa Burdino, Maria Grazia Milia, Patrizia Caligiuri, Vanessa De Pace, Valentina Ricucci, Alexander Domnich, Simona Boccotti, Leoni Maria Cristina, Giuliana Lo Cascio, Salvatore Rubino, Vincenzo Lai, Giulia Rocca, Rosalba Govoni, Giuseppe Mancuso, Roberta Campagna, Laura Mazzuti, Giuseppe Oliveto, Ombretta Turriziani, Laura Campogiani, Mirko Compagno, Luigi Coppola, Angela Maria Antonia Crea, Giuseppe De Simone, Andrea Di Lorenzo, Ludovica Ferrari, Marco Iannetta, Vincenzo Malagnino, Tiziana Mulas, Benedetta Rossi, Ilaria Spalliera, Simona Tedde, Elisabetta Teti, Pietro Vitale, Marta Zordan, Eugenio Milano, Antonella Lagioia, Rosa Gallitelli, Mario Starace, Carmine Minichini, Alessia Di Fraia, Maddalena Schioppa, Rita Greco, Anna Gidari, Maurizio Zazzi, Filippo Dragoni, Laura Li Puma, Silvia Ronchiadin, Luigi Ruggerone, Dario Russignaga, and Scientific Reports, 2022
Loss of ribonuclease DIS3 hampers genome integrity in myeloma by disrupting DNA:RNA hybrid metabolism Ilaria Gritti, Veronica Basso, Darawan Rinchai, Federica Corigliano, Silvia Pivetti, Marco Gaviraghi, Dalia Rosano, Davide Mazza, Sara Barozzi, Marco Roncador, Giovanni Parmigiani, Gaelle Legube, Dario Parazzoli, Davide Cittaro, Davide Bedognetti, Anna Mondino, Simona Segalla, Giovanni Tonon EMBO Journal, 2022
Longitudinal analysis of T cell receptor repertoires reveals shared patterns of antigen-specific response to SARS-CoV-2 infection Rachel M. Gittelman, Enrico Lavezzo, Thomas M. Snyder, H. Jabran Zahid, Cara L. Carty, Rebecca Elyanow, Sudeb Dalai, Ilan Kirsch, Lance Baldo, Laura Manuto, Elisa Franchin, Claudia Del Vecchio, Monia Pacenti, Caterina Boldrin, Margherita Cattai, Francesca Saluzzo, Andrea Padoan, Mario Plebani, Fabio Simeoni, Jessica Bordini, Nicola I. Lorè, Dejan Lazarević, Daniela M. Cirillo, Paolo Ghia, Stefano Toppo, Jonathan M. Carlson, Harlan S. Robins, Andrea Crisanti, Giovanni Tonon Jci Insight, 2022
Chromatin Velocity reveals epigenetic dynamics by single-cell profiling of heterochromatin and euchromatin Martina Tedesco, Francesca Giannese, Dejan Lazarević, Valentina Giansanti, Dalia Rosano, Silvia Monzani, Irene Catalano, Elena Grassi, Eugenia R. Zanella, Oronza A. Botrugno, Leonardo Morelli, Paola Panina Bordignon, Giulio Caravagna, Andrea Bertotti, Gianvito Martino, Luca Aldrighetti, Sebastiano Pasqualato, Livio Trusolino, Davide Cittaro, Giovanni Tonon Nature Biotechnology, 2022
Rapid SARS-CoV-2 Intra-Host and Within-Household Emergence of Novel Haplotypes Laura Manuto, Marco Grazioli, Andrea Spitaleri, Paolo Fontana, Luca Bianco, Luigi Bertolotti, Martina Bado, Giorgia Mazzotti, Federico Bianca, Francesco Onelia, Giovanni Lorenzin, Fabio Simeoni, Dejan Lazarevic, Elisa Franchin, Claudia Del Vecchio, Ilaria Dorigatti, Giovanni Tonon, Daniela Maria Cirillo, Enrico Lavezzo, Andrea Crisanti, Stefano Toppo Viruses, 2022
Radiomic and gEnomic approaches for the enhanced DIagnosis of clear cell REnal Cancer (REDIRECt): a translational pilot methodological study Francesco Cianflone, Dejan Lazarevic, Anna Palmisano, Giuseppe Fallara, Alessandro Larcher, Massimo Freschi, Giacomo Dell’Antonio, Giulia Maria Scotti, Marco J. Morelli, Anna Maria Ferrara, Francesco Trevisani, Alessandra Cinque, Antonio Esposito, Alberto Briganti, Carlo Tacchetti, Claudio Doglioni, Alessandro del Maschio, Francesco de Cobelli, Roberto Bertini, Andrea Salonia, Francesco Montorsi, Giovanni Tonon, Umberto Capitanio Translational Andrology and Urology, 2022
JunB is a key regulator of multiple myeloma bone marrow angiogenesis Fengjuan Fan, Stefano Malvestiti, Sonia Vallet, Judith Lind, Jose Manuel Garcia-Manteiga, Eugenio Morelli, Qinyue Jiang, Anja Seckinger, Dirk Hose, Hartmut Goldschmidt, Andreas Stadlbauer, Chunyan Sun, Heng Mei, Martin Pecherstorfer, Latifa Bakiri, Erwin F. Wagner, Giovanni Tonon, Martin Sattler, Yu Hu, Pierfrancesco Tassone, Dirk Jaeger, Klaus Podar Leukemia, 2021
Chest CT in the emergency department for suspected COVID-19 pneumonia Anna Palmisano, Giulia Maria Scotti, Davide Ippolito, Marco J. Morelli, Davide Vignale, Davide Gandola, Sandro Sironi, Francesco De Cobelli, Luca Ferrante, Marzia Spessot, Giovanni Tonon, Carlo Tacchetti, Antonio Esposito Radiologia Medica, 2021
MATRIGEL CAPILLARITY-DRIVEN FILLING IN OPEN MICROFLUIDICS FOR HIGH-THROUGHPUT DRUG SCREENING ON 3D PATIENT DERIVED ORGANOIDS CULTURES Microtas 2021 25th International Conference on Miniaturized Systems for Chemistry and Life Sciences, 2021
MSH6 gene pathogenic variant identified in familial pancreatic cancer in the absence of colon cancer Alessandro Mannucci, Raffaella A. Zuppardo, Stefano Crippa, Paola Carrera, Maria G. Patricelli, Annalisa Russo Raucci, Federica Calabrese, Dejan Lazarevic, Francesca Giannese, Giovanni Tonon, Maurizio Ferrari, Pier A. Testoni, Giulia Martina Cavestro European Journal of Gastroenterology and Hepatology, 2020
Microbiota-driven interleukin-17-producing cells and eosinophils synergize to accelerate multiple myeloma progression Arianna Calcinotto, Arianna Brevi, Marta Chesi, Roberto Ferrarese, Laura Garcia Perez, Matteo Grioni, Shaji Kumar, Victoria M. Garbitt, Meaghen E. Sharik, Kimberly J. Henderson, Giovanni Tonon, Michio Tomura, Yoshihiro Miwa, Enric Esplugues, Richard A. Flavell, Samuel Huber, Filippo Canducci, Vincent S. Rajkumar, P. Leif Bergsagel, Matteo Bellone Nature Communications, 2018
UTX/KDM6A Loss Enhances the Malignant Phenotype of Multiple Myeloma and Sensitizes Cells to EZH2 inhibition Teresa Ezponda, Daphné Dupéré-Richer, Christine M. Will, Eliza C. Small, Nobish Varghese, Tej Patel, Behnam Nabet, Relja Popovic, Jon Oyer, Marinka Bulic, Yupeng Zheng, Xiaoxiao Huang, Mrinal Y. Shah, Sayantan Maji, Alberto Riva, Manuela Occhionorelli, Giovanni Tonon, Neil Kelleher, Jonathan Keats, Jonathan D. Licht Cell Reports, 2017
Transcription factor TLX1 controls retinoic acid signaling to ensure spleen development Elisa Lenti, Diego Farinello, Kazunari K. Yokoyama, Dmitry Penkov, Laura Castagnaro, Giovanni Lavorgna, Kenly Wuputra, Lisa L. Sandell, Naomi E. Butler Tjaden, Francesca Bernassola, Nicoletta Caridi, Anna De Antoni, Michael Wagner, Katja Kozinc, Karen Niederreither, Francesco Blasi, Diego Pasini, Gregor Majdic, Giovanni Tonon, Paul A. Trainor, Andrea Brendolan Journal of Clinical Investigation, 2016
Chromogranin a is preferentially cleaved into proangiogenic peptides in the bone marrow of multiple myeloma patients Mimma Bianco, Anna Maria Gasparri, Barbara Colombo, Flavio Curnis, Stefania Girlanda, Maurilio Ponzoni, Maria Teresa Sabrina Bertilaccio, Arianna Calcinotto, Angelina Sacchi, Elisabetta Ferrero, Marina Ferrarini, Marta Chesi, P. Leif Bergsagel, Matteo Bellone, Giovanni Tonon, Fabio Ciceri, Magda Marcatti, Federico Caligaris-Cappio, Angelo Corti Cancer Research, 2016
Insight on Colorectal Carcinoma Infiltration by Studying Perilesional Extracellular Matrix Manuela Nebuloni, Luca Albarello, Annapaola Andolfo, Cinzia Magagnotti, Luca Genovese, Irene Locatelli, Giovanni Tonon, Erika Longhi, Pietro Zerbi, Raffaele Allevi, Alessandro Podestà, Luca Puricelli, Paolo Milani, Armando Soldarini, Andrea Salonia, Massimo Alfano Scientific Reports, 2016
HIF-1α regulates the interaction of chronic lymphocytic leukemia cells with the tumor microenvironment Roberta Valsecchi, Nadia Coltella, Daniela Belloni, Manfredi Ponente, Elisa ten Hacken, Cristina Scielzo, Lydia Scarfò, Maria Teresa Sabrina Bertilaccio, Paola Brambilla, Elisa Lenti, Filippo Martinelli Boneschi, Andrea Brendolan, Elisabetta Ferrero, Marina Ferrarini, Paolo Ghia, Giovanni Tonon, Maurilio Ponzoni, Federico Caligaris-Cappio, Rosa Bernardi Blood, 2016
Histone demethylase JARID1C inactivation triggers genomic instability in sporadic renal cancer Beatrice Rondinelli, Dalia Rosano, Elena Antonini, Michela Frenquelli, Laura Montanini, DaChuan Huang, Simona Segalla, Kosuke Yoshihara, Samir B. Amin, Dejan Lazarevic, Bin Tean The, Roel G.W. Verhaak, P. Andrew Futreal, Luciano Di Croce, Lynda Chin, Davide Cittaro, Giovanni Tonon Journal of Clinical Investigation, 2015
p63 sustains self-renewal of mammary cancer stem cells through regulation of Sonic Hedgehog signaling Elisa Maria Memmi, Anna Giulia Sanarico, Arianna Giacobbe, Angelo Peschiaroli, Valentina Frezza, Angelo Cicalese, Federica Pisati, Daniela Tosoni, Huiqing Zhou, Giovanni Tonon, Alexey Antonov, Gerry Melino, Pier Giuseppe Pelicci, Francesca Bernassola Proceedings of the National Academy of Sciences of the United States of America, 2015
Contrasting roles of histone 3 lysine 27 demethylases in acute lymphoblastic leukaemia Panagiotis Ntziachristos, Aristotelis Tsirigos, G. Grant Welstead, Thomas Trimarchi, Sofia Bakogianni, Luyao Xu, Evangelia Loizou, Linda Holmfeldt, Alexandros Strikoudis, Bryan King, Jasper Mullenders, Jared Becksfort, Jelena Nedjic, Elisabeth Paietta, Martin S. Tallman, Jacob M. Rowe, Giovanni Tonon, Takashi Satoh, Laurens Kruidenier, Rab Prinjha, Shizuo Akira, Pieter Van Vlierberghe, Adolfo A. Ferrando, Rudolf Jaenisch, Charles G. Mullighan, Iannis Aifantis Nature, 2014
Rescue of Hippo coactivator YAP1 triggers DNA damage-induced apoptosis in hematological cancers Francesca Cottini, Teru Hideshima, Chunxiao Xu, Martin Sattler, Martina Dori, Luca Agnelli, Elisa ten Hacken, Maria Teresa Bertilaccio, Elena Antonini, Antonino Neri, Maurilio Ponzoni, Magda Marcatti, Paul G Richardson, Ruben Carrasco, Alec C Kimmelman, Kwok-Kin Wong, Federico Caligaris-Cappio, Giovanni Blandino, W Michael Kuehl, Kenneth C Anderson, Giovanni Tonon Nature Medicine, 2014
Erratum: Telomere dysfunction induces metabolic and mitochondrial compromise (Nature (2011) 470 (359-365)) Ergün Sahin, Simona Colla, Marc Liesa, Javid Moslehi, Florian L. Müller, Mira Guo, Marcus Cooper, Darrell Kotton, Attila J. Fabian, Carl Walkey, Richard S. Maser, Giovanni Tonon, Friedrich Foerster, Robert Xiong, Y. Alan Wang, Sachet A. Shukla, Mariela Jaskelioff, Eric S. Martin, Timothy P. Heffernan, Alexei Protopopov, Elena Ivanova, John E. Mahoney, Maria Kost-Alimova, Samuel R. Perry, Roderick Bronson, Ronglih Liao, Richard Mulligan, Orian S. Shirihai, Lynda Chin, Ronald A. DePinho Nature, 2011
Pancreatic cancers require autophagy for tumor growth Shenghong Yang, Xiaoxu Wang, Gianmarco Contino, Marc Liesa, Ergun Sahin, Haoqiang Ying, Alexandra Bause, Yinghua Li, Jayne M. Stommel, Giacomo Dell'Antonio, Josef Mautner, Giovanni Tonon, Marcia Haigis, Orian S. Shirihai, Claudio Doglioni, Nabeel Bardeesy, Alec C. Kimmelman Genes and Development, 2011
Telomere dysfunction induces metabolic and mitochondrial compromise Ergün Sahin, Simona Colla, Marc Liesa, Javid Moslehi, Florian L. Müller, Mira Guo, Marcus Cooper, Darrell Kotton, Attila J. Fabian, Carl Walkey, Richard S. Maser, Giovanni Tonon, Friedrich Foerster, Robert Xiong, Y. Alan Wang, Sachet A. Shukla, Mariela Jaskelioff, Eric S. Martin, Timothy P. Heffernan, Alexei Protopopov, Elena Ivanova, John E. Mahoney, Maria Kost-Alimova, Samuel R. Perry, Roderick Bronson, Ronglih Liao, Richard Mulligan, Orian S. Shirihai, Lynda Chin, Ronald A. DePinho Nature, 2011
Correction of β-thalassemia major by gene transfer in haematopoietic progenitors of pediatric patients Emanuela Anna Roselli, Riccardo Mezzadra, Marta Claudia Frittoli, Giulietta Maruggi, Erika Biral, Fulvio Mavilio, Fabrizio Mastropietro, Antonio Amato, Giovanni Tonon, Chiara Refaldi, Maria Domenica Cappellini, Marco Andreani, Guido Lucarelli, Maria Grazia Roncarolo, Sarah Marktel, Giuliana Ferrari EMBO Molecular Medicine, 2010
CS1 promotes multiple myeloma cell adhesion, clonogenic growth, and tumorigenicity via c-maf-mediated interactions with bone marrow stromal cells (Blood (2009) 113, 18, (4309-4318)) Blood, 2010
Somatic mutations of the histone H3K27 demethylase gene UTX in human cancer Gijs van Haaften, Gillian L Dalgliesh, Helen Davies, Lina Chen, Graham Bignell, Chris Greenman, Sarah Edkins, Claire Hardy, Sarah O'Meara, Jon Teague, Adam Butler, Jonathan Hinton, Calli Latimer, Jenny Andrews, Syd Barthorpe, Dave Beare, Gemma Buck, Peter J Campbell, Jennifer Cole, Simon Forbes, Mingming Jia, David Jones, Chai Yin Kok, Catherine Leroy, Meng-Lay Lin, David J McBride, Mark Maddison, Simon Maquire, Kirsten McLay, Andrew Menzies, Tatiana Mironenko, Lee Mulderrig, Laura Mudie, Erin Pleasance, Rebecca Shepherd, Raffaella Smith, Lucy Stebbings, Philip Stephens, Gurpreet Tang, Patrick S Tarpey, Rachel Turner, Kelly Turrell, Jennifer Varian, Sofie West, Sara Widaa, Paul Wray, V Peter Collins, Koichi Ichimura, Simon Law, John Wong, Siu Tsan Yuen, Suet Yi Leung, Giovanni Tonon, Ronald A DePinho, Yu-Tzu Tai, Kenneth C Anderson, Richard J Kahnoski, Aaron Massie, Sok Kean Khoo, Bin Tean Teh, Michael R Stratton, P Andrew Futreal Nature Genetics, 2009
p53 and Pten control neural and glioma stem/progenitor cell renewal and differentiation Hongwu Zheng, Haoqiang Ying, Haiyan Yan, Alec C. Kimmelman, David J. Hiller, An-Jou Chen, Samuel R. Perry, Giovanni Tonon, Gerald C. Chu, Zhihu Ding, Jayne M. Stommel, Katherine L. Dunn, Ruprecht Wiedemeyer, Mingjian J. You, Cameron Brennan, Y. Alan Wang, Keith L. Ligon, Wing H. Wong, Lynda Chin, Ronald A. DePinho Nature, 2008
Somatic mutations affect key pathways in lung adenocarcinoma Li Ding, Gad Getz, David A. Wheeler, Elaine R. Mardis, Michael D. McLellan, Kristian Cibulskis, Carrie Sougnez, Heidi Greulich, Donna M. Muzny, Margaret B. Morgan, Lucinda Fulton, Robert S. Fulton, Qunyuan Zhang, Michael C. Wendl, Michael S. Lawrence, David E. Larson, Ken Chen, David J. Dooling, Aniko Sabo, Alicia C. Hawes, Hua Shen, Shalini N. Jhangiani, Lora R. Lewis, Otis Hall, Yiming Zhu, Tittu Mathew, Yanru Ren, Jiqiang Yao, Steven E. Scherer, Kerstin Clerc, Ginger A. Metcalf, Brian Ng, Aleksandar Milosavljevic, Manuel L. Gonzalez-Garay, John R. Osborne, Rick Meyer, Xiaoqi Shi, Yuzhu Tang, Daniel C. Koboldt, Ling Lin, Rachel Abbott, Tracie L. Miner, Craig Pohl, Ginger Fewell, Carrie Haipek, Heather Schmidt, Brian H. Dunford-Shore, Aldi Kraja, Seth D. Crosby, Christopher S. Sawyer, Tammi Vickery, Sacha Sander, Jody Robinson, Wendy Winckler, Jennifer Baldwin, Lucian R. Chirieac, Amit Dutt, Tim Fennell, Megan Hanna, Bruce E. Johnson, Robert C. Onofrio, Roman K. Thomas, Giovanni Tonon, Barbara A. Weir, Xiaojun Zhao, Liuda Ziaugra, Michael C. Zody, Thomas Giordano, Mark B. Orringer, Jack A. Roth, Margaret R. Spitz, Ignacio I. Wistuba, Bradley Ozenberger, Peter J. Good, Andrew C. Chang, David G. Beer, Mark A. Watson, Marc Ladanyi, Stephen Broderick, Akihiko Yoshizawa, William D. Travis, William Pao, Michael A. Province, George M. Weinstock, Harold E. Varmus, Stacey B. Gabriel, Eric S. Lander, Richard A. Gibbs, Matthew Meyerson, Richard K. Wilson Nature, 2008
The Differentiation and Stress Response Factor XBP-1 Drives Multiple Myeloma Pathogenesis Daniel R. Carrasco, Kumar Sukhdeo, Marina Protopopova, Raktim Sinha, Miriam Enos, Daniel E. Carrasco, Mei Zheng, Mala Mani, Joel Henderson, Geraldine S. Pinkus, Nikhil Munshi, James Horner, Elena V. Ivanova, Alexei Protopopov, Kenneth C. Anderson, Giovanni Tonon, Ronald A. DePinho Cancer Cell, 2007
K-ras activation generates an inflammatory response in lung tumors H Ji, A M Houghton, T J Mariani, S Perera, C B Kim, R Padera, G Tonon, K McNamara, L A Marconcini, A Hezel, N El-Bardeesy, R T Bronson, D Sugarbaker, R S Maser, S D Shapiro, K-K Wong Oncogene, 2006
High-resolution genomic profiles define distinct clinico-pathogenetic subgroups of multiple myeloma patients Daniel R. Carrasco, Giovanni Tonon, Yongsheng Huang, Yunyu Zhang, Raktim Sinha, Bin Feng, James P. Stewart, Fenghuang Zhan, Deepak Khatry, Marina Protopopova, Alexei Protopopov, Kumar Sukhdeo, Ichiro Hanamura, Owen Stephens, Bart Barlogie, Kenneth C. Anderson, Lynda Chin, John D. Shaughnessy, Cameron Brennan, Ronald A. DePinho Cancer Cell, 2006
High-resolution genomic profiles of human lung cancer Giovanni Tonon, Kwok-Kin Wong, Gautam Maulik, Cameron Brennan, Bin Feng, Yunyu Zhang, Deepak B. Khatry, Alexei Protopopov, Mingjian James You, Andrew J. Aguirre, Eric S. Martin, Zhaohui Yang, Hongbin Ji, Lynda Chin, Ronald A. DePinho Proceedings of the National Academy of Sciences of the United States of America, 2005
