Description
This line of activity is focused on analyzing the interactions between immunity and cancer at two levels, systemic and of the neoplastic microenvironment, in particular as regards the development and evolution of the antitumor response, the avoidance mechanisms put in place by the neoplasm and the genetic / metabolic / cellular aspects underlying these events. A further aspect consists in identifying and implementing therapeutic solutions based on the most advanced technologies in the immune field and on the stimulation of the immunoeffective components, with the overall goal of restoring the full efficiency of the immune system and enhancing its anticancer capabilities.
Background
Cancer immunology is an interdisciplinary field of biology / medicine that aims to understand the changes occurring in the immune system during tumor development and progression. As it describes the interactions between immune cells and cancer cells, understanding these interactions is important for the development of new anticancer therapies. In this context, cancer immunotherapy is a rapidly evolving concept, so much so that it is defined as the “fifth pillar” of cancer therapy, in addition to radiotherapy, chemotherapy, surgery and targeted therapies. In this regard, the continuous expansion of the use of so-called immunological checkpoint inhibitors (ICI), monoclonal antibodies (mAb) able to prevent the feedback inhibition of activated T cells and to stimulate protective and therapeutic cellular T responses directed against neoantigens highly tumor-specific, also paves the way for further research areas such as:
- the profiling of the neoplastic component, for the identification of new targets, and of the immune infiltrate, for the characterization of the determinants of protection / efficacy;
- the development of strictly personalized immunotherapeutic interventions;
- the study of combinatorial therapies between ICI and pharmacological / nanotechnological, biotechnological, vaccine and / or adoptive therapies with T cells, capable of promoting the expansion and functionality of effector populations.
Rationale
The use of ICI in current oncological practice is literally revolutionizing the expectations of clinical outcome in many neoplastic areas, but on the other hand it increasingly imposes the identification of predictive biomarkers of response able to guide the selection of patients, in order to rationalize and personalize therapies keeping in mind both toxicity and cost-effectiveness profiles for the National Health System. On the other hand, the most recent evolutions in genomics, proteomics, metabolomics, etc., allow the acquisition of fundamental information to really envision the implementation of immunotherapeutic strategies at a strictly individual level. Finally, we must not forget the emerging role of adoptive cell therapy, in particular CAR-T, which from the haematological sector is rapidly finding experimental applications in solid tumors and in which IOV is particularly active, even with innovative effector cell populations.
Global Goals
Globally, the research line has multiple objectives, such as:
- the genetic / metabolic profiling, even single cell, of the neoplastic and infiltrative component of tumors potentially target of immunological therapies;
- cellular immunoprofilation at the peripheral level and in the tumor-stroma context with innovative techniques (multiparametric flow cytometry, multiplex fluorescence immunohistochemistry);
- the development of in vitro and in vivo experimental models for the understanding of tumor-immune system interactions and for the development and evaluation of newly conceived immunotherapeutic approaches.
Expected and measurable results over the three-year period
During the three-year period it is expected:
- to increase by at least 25% the number of profiled samples both at the genomic and immunophenotypic level and to arrive at a full integration between the data obtained in next generation sequencing, digital pathology and correlated with computerized clinical record, with the aim of identifying and validate new prognostic or predictive biomarkers of response;
- to increase by 20% the studies aimed at understanding the mechanisms and mediators involved in the avoidance of the immune response by the tumor, as well as possible reversal interventions;
- to enhance preclinical studies of active and adoptive immunotherapy, in order to identify at least two studies capable of being effectively translated into phase 1 clinical trials.
Titolo | Testata | IF grezzo | Autori |
---|---|---|---|
Mitochondrial fission links ECM mechanotransduction to metabolic redox homeostasis and metastatic chemotherapy resistance | NATURE CELL BIOLOGY | 28,21 | Patrizia Romani, Nunzia Nirchio, Mattia Arboit, Barbieri Vito, tosi anna, Federica Michielin, Soichi Shibuya, Thomas Benoist, Danchen Wu, Charles Colin Thomas Hindmarch, Monica Giomo, Anna Urciuolo, Flavia Giamogante, Antonella Roveri, Marco Montagner, Probir Chakravarty, Tito Calì, Nicola Elvassore, Stephen L. Archer, Paolo De Coppi, ROSATO ANTONIO, Graziano Martello, Sirio Dupont |
Functional mapping of PHF6 complexes in chromatin remodeling, replication dynamics, and DNA repair | BLOOD | 25,67 | Silvia Alvarez, Ana C. da Silva Almeida, Robert Albero, Mayukh Biswas, Angelica Barreto-Galvez, Thomas S. Gunning, Anam Shaikh, Tomas Aparicio, Agnieszka Wendorff, Piovan Erich, Pieter Van Vlierberghe, Steven Gygi, Jean Gautier, Advaitha Madireddy, Adolfo A. Ferrando |
Tyd LGL LEUKEMIA IDENTIFIES A SUBSET WITH MORE SYMPTOMATIC DISEASE: ANALYSIS OF AN INTERNATIONAL COHORT OF 137 PATIENTS | BLOOD | 25,67 | G Barilà, Grassi Angela, H Cheon, G Semenzato, R Zambello |
Single-cell analyses reveal YAP/TAZ as regulators of stemness and cell plasticity in Glioblastoma | Nature Cancer | 23,18 | Martina Castellan, Alberto Guarnieri, Atsushi Fujimura, Francesca Zanconato, Giusy Battilana, Tito Panciera, Hanna Lucie Sladitschek, Paolo Contessotto, Anna Citron, Andrea Grilli, Oriana Romano, Silvio Bicciato, matteo fassan, Elena Porcù, ROSATO ANTONIO, Michelangelo Cordenonsi, Stefano Piccolo |
Clinical efficacy and safety of angiogenesis inhibitors: sex differences and current challenges | CARDIOVASCULAR RESEARCH | 14,24 | Andrea Cignarella, Gian Paolo Fadini, Chiara Bolego, Lucia Trevisi, Carlotta Boscaro, Viola Sanga, Teresa Maria Seccia, ROSATO ANTONIO, Gian Paolo Rossi, Matthias Barton |
Phosphorylation of SHP2 at Tyr62 Enables Acquired Resistance to SHP2 Allosteric Inhibitors in FLT3-ITD-Driven AML | CANCER RESEARCH | 13,31 | Anamarija Pfeiffer , Giulia Franciosa , Marie Locard-Paulet , Piga Ilaria, Kristian Reckzeh , Vidyasiri Vemulapalli , Stephen C. Blacklow , Kim Theilgaard-Mönch , Lars J. Jensen , Jesper V. Olsen |
A comprehensive profiling of the immune microenvironment of breast cancer brain metastases | NEURO-ONCOLOGY | 13,03 | Griguolo Gaia, Anna Tosi, DIECI MARIA VITTORIA, Susan Fineberg, Rossi Valentina, Annavera Ventura, Michele Bottosso, Luc Bauchet, Federica Miglietta, Jack Jacob, Valerie Rigau, FASSAN MATTEO, William Jacot, Pierfranco Conte, ROSATO ANTONIO, Amelie Darlix, Guarneri Valentina |
Colorectal cancer development is affected by the ECM molecule EMILIN-2 hinging on macrophage polarization via the TLR-4/MyD88 pathway | JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH | 12,66 | Eva Andreuzzi, Albina Fejza, Maurizio Polano, Evelina Poletto, Lucrezia Camicia, Greta Carobolante, Giulia Tarticchio, Federico Todaro, Emma Di Carlo, Scarpa Melania, Marco Scarpa, Alice Paulitti, Alessandra Capuano, Vincenzo Canzonieri, Stefania Maiero, Mara Fornasarig, Renato Cannizzaro, Roberto Doliana, Alfonso Colombatti, Paola Spessotto, Maurizio Mongiat |
The immune microenvironment of HPV-positive and HPV-negative oropharyngeal squamous cell carcinoma: a multiparametric quantitative and spatial analysis unveils a rationale to target treatment-naïve tumors with immune checkpoint inhibitors | JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH | 12,66 | tosi anna, Beatrice Parisatto, Anna Menegaldo, Giacomo Spinato, Maria Guido, Del Mistro Annarosa, Rossana Bussani, Fabrizio Zanconati, Margherita Tofanelli, Giancarlo Tirelli, Paolo Boscolo-Rizzo, ROSATO ANTONIO |
The complex karyotype landscape in chronic lymphocytic leukemia allows the refinement of the risk of Richter syndrome transformation | Haematologica-The Hematology Journal | 11,05 | Andrea Visentin, Bonaldi Laura, Gian Matteo Rigolin, Francesca Romana Mauro, Martines Annalisa, Federica Frezzato, Stefano Pravato, Leila Romano Gargarella, Maria Antonella Bardi, Maurizio Cavallari, Eleonora Volta, Francesco Cavazzini, Mauro Nanni, Monica Facco, Francesco Piazza, Anna Guarini, Robin Foà, Gianpietro Semenzato, Antonio Cuneo, Livio Trentin |
mTOR inhibition downregulates glucose-6-phosphate dehydrogenase and induces ROS-dependent death in T-cell acute lymphoblastic leukemia cells | Redox Biology | 10,79 | Silic-Benussi Micol, Evgenyia Sharova, Ciccarese Francesco, CAVALLARI ILARIA, Vittoria Raimondi, URSO LOREDANA, Alberto Corradin, Harel Kotler, Gloria Scattolin, Barbara Buldini, Samuela Francescato, Giuseppe Basso, Sonia A. Minuzzo, INDRACCOLO STEFANO, D’Agostino Donna Mia, Ciminale Vincenzo |
Clinical profile and mortality of Sars-Cov-2 infection in cancer patients across two pandemic time periods (Feb 2020¿Sep 2020; Sep 2020¿May 2021) in the Veneto Oncology Network: The ROVID study | EUROPEAN JOURNAL OF CANCER | 10,00 | DIECI MARIA VITTORIA, Giuseppe Azzarello, zagonel vittorina, Franco Bassan, Stefania Gori, Giuseppe Aprile, chiarion sileni vanna, Lonardi Sara, Cristina Oliani, Marta Zaninelli, Rita Chiari, Adolfo Favaretto, Alberto Pavan, Di Liso Elisabetta, Mioranza Eleonora, Alessandra Baldoni, bergamo francesca, MARUZZO MARCO, Stamatia Ziampiri, Alessandro Inno, Filomena Graziani, Giusy Sinigaglia, Michele Celestino, Conte Pierfranco, Guarneri Valentina |
Durvalumab consolidation in patients with unresectable stage III non-small cell lung cancer with driver genomic alterations | EUROPEAN JOURNAL OF CANCER | 10,00 | Mariona Riudavets, Edouard Auclin, Miguel Mosteiro, Naomi Dempsey, Margarita Majem, Riccardo Lobefaro, Rafael López-Castro, Joaquim Bosch-Barrera, Sara Pilotto, Elena Escalera, Marco Tagliamento, Joaquin Mosquera, Gerard Zalcman, Frank Aboubakar-Nana, Santiago Ponce, DAL MASO ALESSANDRO, Martina Spotti, Xabier Mielgo-Rubio, Elodie Mussat, Roxana Reyes, José-Carlos Benítez, Lorena Lupinacci, Boris Duchemann, Andrea De Giglio, Juan Blaquier, Clarisse Audigier-Valette, Matthias Scheffler, Ernest Nadal, Gilberto Lopes, Diego Signorelli, Rosario Garcia-Campelo, Jessica Menis, Virginia Bluthgen, Marc Campayo, Gonzalo Recondo, Benjamin Besse, David Planchard, Laura Mezquita |
Risks of breast and ovarian cancer for women harboring pathogenic missense variants in BRCA1 and BRCA2 compared with those harboring protein truncating variants | GENETICS IN MEDICINE | 8,86 | Hongyan Li, Christoph Engel, Miguel de la Hoya, Paolo Peterlongo, Drakoulis Yannoukakos, Luca Livraghi, Paolo Radice, Mads Thomassen, Thomas V.O. Hansen, Anne-Marie Gerdes, Henriette R. Nielsen, Sandrine M. Caputo, Alberto Zambelli, Ake Borg, Angela Solano, Abigail Thomas, Michael T. Parsons, Antonis C. Antoniou, Goska Leslie, Xin Yang, Georgia Chenevix-Trench, Trinidad Caldes, Ava Kwong, Inge Søkilde Pedersen, Charlotte K. Lautrup, Esther M. John, Mary Beth Terry, John L. Hopper, Melissa C. Southey, Irene L. Andrulis, Marc Tischkowitz, Ramunas Janavicius, Susanne E. Boonen, Lone Kroeldrup, Liliana Varesco, Ute Hamann, Ana Vega, Edenir I. Palmero, Judy Garber, Montagna Marco, Christi J. Van Asperen, Lenka Foretova, Mark H. Greene, Tina Selkirk, Pal Moller, Amanda E. Toland, Susan M. Domchek, Paul A. James, Heather Thorne, Diana M. Eccles, Sarah M. Nielsen, Siranoush Manoukian, Barbara Pasini, Maria A. Caligo, Conxi Lazaro, Judy Kirk, Barbara Wappenschmidt, Amanda B. Spurdle, Fergus J. Couch, Rita Schmutzler, David E. Goldgar |
Myeloid Diagnostic and Prognostic Markers of Immune Suppression in the Blood of Glioma Patients | Frontiers in Immunology | 8,79 | Del Bianco Paola, Laura Pinton, Sara Magri, Stefania Canè, Elena Masetto, Daniela Basso, Marta Padovan, Francesco Volpin, Domenico d’Avella, LOMBARDI GIUSEPPE, zagonel vittorina, Vincenzo Bronte, Alessandro Della Puppa, Mandruzzato Susanna |