Supervisor

Prof. Antonio Rosato

Description

This research line aims to analyze the interactions between immunity and cancer, and to identify, propose, and implement therapeutic solutions based on the stimulation of the effector components of the immune system. At IOV, these aspects will be studied through:

  • the evaluation in experimental models of the efficacy of new vaccine formulations, of adoptive immunotherapy approaches, and of pharmacological interventions aimed at restoring the full efficiency of the immune system;
  • the analysis and identification of new immune and prognostic and / or predictive biomarkers in the context of the current clinical activity and the experiments already underway.

Background

Immunotherapy of tumors is experiencing an important phase of cultural renaissance, particularly thanks to the recent introduction, into the armament of cancer therapies, of immune checkpoint inhibitors (ICI) and monoclonal antibodies (mAb) able to prevent the feedback inhibition of activated T cell, and to stimulate protective and therapeutic T cell responses directed against tumor neoantigens deriving from mutations of normal neoplastic cell proteins, which behave as highly tumor-specific antigens. These observations present potentially important breakthroughs, as they allow us to envision, on the one hand, possible personalized immunotherapeutic interventions, and, on the other, to conceive combinatorial therapies of ICI and vaccines and / or adoptive therapies with T cells able to favor the expansion and functionality of highly effective effector populations.

Rationale

The introduction of ICIs in current oncology practice is dramatically changing the expectations of clinical outcomes for some tumor types; however, it also imposes, in an equally dramatic way, the identification of predictive biomarkers of response capable of guiding patient selection, in order to rationalize and personalize therapies in view of both toxicity profiles and cost effectiveness. On the other hand, vaccine and cellular immunotherapeutic strategies are virtually unrecognized in our country on the basis of cultural and research deficiencies, and of technological, regulatory, and economic difficulties to implement these approaches, in particular, the engineering of T cells. Moreover, a strategic plan to develop adequate facilities for the manufacture of cellular drugs for therapeutic use is lacking.

Global goals

  • to obtain immunogenetic profiles of neoplasms of immunological relevance;
  • to obtain cellular immunoprofiles at the peripheral level and in the tumor-stroma (immunoscore);
  • to develop preclinical models for the experimentation of innovative immunotherapies.

Expected results

Expected results during the three-year period include: a) the implementation of an integrated immunoprofiling platform based on NGS, cytometry, and digital pathology able to identify and validate new prognostic or predictive biomarkers; b) the strengthening of preclinical adoptive immunotherapy studies to be effectively transferred into phase 1 clinical studies.

Top 15 pubblicazioni 2019 linea 2
TitoloAutori Rivista IF grezzo
Tumor-Infiltrating Lymphocytes and Prognosis: A Pooled Individual Patient Analysis of Early-Stage Triple-Negative Breast CancersLoi S, Drubay D, Adams S, Pruneri G, Francis PA, Lacroix-Triki M, Joensuu H, Dieci Maria Vittoria, Badve S, Demaria S, Gray R, Munzone E, Lemonnier J, Sotirou C, Piccart MJ, Kellokumpu-Lehtinen PL, Vingiani A, Gray K, Andre F, Denkert C, Salgado R, Michiels SJOURNAL OF CLINICAL ONCOLOGY28.349
Sustained Type I interferon signaling as a mechanism of resistance to PD-1 blockadeJacquelot Nicolas, Yamazaki Takahiro, Roberti Maria P, Duong Connie P M, Andrews Miles C, Verlingue Loic, Ferrere Gladys, Becharef Sonia, Vétizou Marie, Daillère Romain, Messaoudene Meriem, Enot David P, Stoll Gautier, Ugel Stefano, Marigo Ilaria, Foong Ngiow Shin, Marabelle Aurélien, Prevost-Blondel Armelle, Gaudreau Pierre-Olivier, Gopalakrishnan Vancheswaran, Eggermont Alexander M, Opolon Paule, Klein Christophe, Madonna Gabriele, Ascierto Paolo A, Sucker Antje, Schadendorf Dirk, Smyth Mark J, Soria Jean-Charles, Kroemer Guido, Bronte Vincenzo, Wargo Jennifer, Zitvogel LaurenceCELL RESEARCH17.848
Association of tumor-infiltrating lymphocytes with distant disease-free survival in the ShortHER randomized adjuvant trial for patients with early HER2+ breast cancerDieci Maria Vittoria, Conte Pierfranco, Bisagni G., Brandes A.A., Frassoldati A., Cavanna L., Musolino A., Giotta F., Rimanti A., Garrone O., Bertone E., Cagossi K., Sarti S., Ferro A., Piacentini F., Maiorana A., Maiorana A., Orvieto E., Sanders M., Miglietta F., Balduzzi S., D'Amico R., Guarneri ValentinaANNALS OF ONCOLOGY14.196
Prognostic value of tumor-infiltrating lymphocytes in patients with early-stage triple-negative breast cancers (TNBC) who did not receive adjuvant chemotherapyPark J H, Jonas S F, Bataillon G, Criscitiello C, Salgado R, Loi S, Viale G, Lee H J, Dieci Maria Vittoria, Kim S-B, Vincent-Salomon A, Curigliano G, André F, Michiels SANNALS OF ONCOLOGY14.196
Immunosuppression by monocytic myeloid-derived suppressor cells in patients with pancreatic ductal carcinoma is orchestrated by STAT3Trovato Rosalinda, Fiore Alessandra, Sartori Sara, Canè Stefania, Giugno Rosalba, Cascione Luciano, Paiella Salvatore, Salvia Roberto, De Sanctis Francesco, Poffe Ornella, Anselmi Cristina, Hofer Francesca, Sartoris Silvia, Piro Geny, Carbone Carmine, Carbone Carmine, Corbo Vincenzo, Lawlor Rita, Solito Samantha, Pinton Laura, Mandruzzato Susanna, Bassi Claudio, Scarpa Aldo, Bronte Vincenzo, Ugel StefanoJournal for ImmunoTherapy of Cancer8.728
Interaction of host immunity with HER2-targeted treatment and tumor heterogeneity in HER2-positive breast cancerGriguolo Gaia, Pascual Tomás, Dieci Maria Vittoria, Guarneri Valentina, Prat AleixJournal for ImmunoTherapy of Cancer8.728
The immune suppressive microenvironment of human gliomas depends on the accumulation of bone marrow-derived macrophages in the center of the lesionPinton Laura, Masetto Elena, Vettore Marina, Solito Samantha, Magri Sara, D'Andolfi Marta, Del Bianco Paola, Lollo Giovanna, Benoit Jean-Pierre, Okada Hideho, Diaz Aaron, Della Puppa Alessandro, Mandruzzato SusannaJournal for ImmunoTherapy of Cancer8.728
Diabetes-Associated Myelopoiesis Drives Stem Cell Mobilopathy Through an OSM-p66Shc Signaling PathwayAlbiero M, Ciciliot S, Tedesco S, Menegazzo L, D'Anna M, Scattolini V, Cappellari R, Zuccolotto G, Rosato Antonio, Cignarella A, Giorgio M, Avogaro A, Fadini GPDIABETES7.199
Inclusion of Platinum Agents in Neoadjuvant Chemotherapy Regimens for Triple-Negative Breast Cancer PatientsDieci Maria Vittoria, Del Mastro Lucia, Cinquini Michela, Montemurro Filippo, Biganzoli Laura, Cortesi Laura, Zambelli Alberto, Criscitiello Carmen, Levaggi Alessia, Conte Benedetta, Calabrese Massimo, Fiorentino Alba, Marchiò Caterina, Tinterri Corrado, Fittipaldo Veronica Andrea, Pappagallo Giovanni, Gori StefaniaCancers6.162
Programmed Cell Death Ligand 1 in Breast Cancer: Technical Aspects, Prognostic Implications, and Predictive ValueMiglietta Federica, Griguolo Gaia, Guarneri Valentina, Dieci Maria VittoriaONCOLOGIST5.252
177Lu-Bombesin-PLGA (paclitaxel): A targeted controlled-release nanomedicine for bimodal therapy of breast cancerGibbens-Bandala Brenda, Morales-Avila Enrique, Ferro-Flores Guillermina, Santos-Cuevas Clara, Melendez Alafort Laura, Trujillo-Nolasco Maydelid, Ocampo-García BlancaMaterials Science & Engineering C-Materials for Biological Applications4.959
The Endless Saga of Monocyte DiversityCanè Stefania, Ugel Stefano, Trovato Rosalinda, Marigo Ilaria, De Sanctis Francesco, Sartoris Silvia, Bronte VincenzoFrontiers in Immunology4.716
A non-covalent antibody complex for the delivery of anti-cancer drugsMaso Katia, montagner isabella monia, Grigoletto Antonella, Schiavon Oddone, Rosato Antonio, Pasut GianfrancoEUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS4.708
Synthesis and characterisation of a new benzamide-containing nitrobenzoxadiazole as a GSTP1-1 inhibitor endowed with high stability to metabolic hydrolysisDi Paolo Veronica, Fulci Chiara, Rotili Dante, Sciarretta Francesca, Lucidi Alessia, Morozzo Della Rocca Blasco, De Luca Anastasia, Rosato Antonio, Quintieri Luigi, Caccuri Anna MariaJOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY4.027
Structure-function relationship of an Urokinase Receptor-derived peptide which inhibits the Formyl Peptide Receptor type 1 activityMinopoli Michele, Polo Andrea, Ragone Concetta, Ingangi Vincenzo, Ciliberto Gennaro, Pessi Antonello, Sarno Sabrina, Budillon Alfredo, Costantini Susan, Carriero Maria VincenzaScientific Reports4.011

Source: IOV Scientific library

Top 15 pubblicazioni 2018 linea 2
TitoloAutoriRivistaIF grezzo
Mechanical cues control mutant p53 stability through a mevalonate-RhoA axisIngallina Eleonora, Sorrentino Giovanni, Bertolio Rebecca, Lisek Kamil, Zannini Alessandro, Azzolin Luca, Severino Luisa Ulloa, Scaini Denis, Mano Miguel, Mantovani Fiamma, Rosato Antonio, Bicciato Silvio, Piccolo Stefano, Del Sal GianninoNATURE CELL BIOLOGY19.064
Malignant pleural mesothelioma immune microenvironment and checkpoint expression correlation with clinical-pathological features and intratumor heterogeneity over timePasello Giulia, Zago Giulia, Lunardi F, Urso L, Kern I, Vlacic G, Grosso F, Mencoboni M, Ceresoli G L, Schiavon M, Pezzuto F, Pavan A, Vuljan S E, Del Bianco Paola, Conte Pierfranco, Rea F, Calabrese FANNALS OF ONCOLOGY13.93
Prognostic implications of residual disease tumor-infiltrating lymphocytes and residual cancer burden in triple negative breast cancer patients after neo-adjuvant chemotherapyLuen S J, Salgado R, Dieci Maria Vittoria, Vingiani A, Curigliano G, Gould R E, Castaneda C, D'Alfonso T, Sanchez J, Cheng E, Andreopoulou E, Castillo M, Adams S, Demaria S, Symmans W F, Michiels S, Loi SANNALS OF ONCOLOGY13.93
Induction of immunosuppressive functions and NF-κB by FLIP in monocytesFiore Alessandra, Ugel Stefano, De Sanctis Francesco, Sandri Sara, Fracasso Giulio, Trovato Rosalinda, Sartoris Silvia, Solito Samantha, Mandruzzato Susanna, Vascotto Fulvia, Hippen Keli L., Mondanelli Giada, Grohmann Ursula, Piro Geny, Carbone Carmine, Melisi Davide, Lawlor Rita T., Scarpa Aldo, Lamolinara Alessia, Iezzi Manuela, Fassan Matteo, Bicciato Silvio, Blazar Bruce R., Sahin Ugur, Murray Peter J., Bronte VincenzoNature Communications12.353
Immunotherapy in SCLC Exceptional Clinical Benefit and Abscopal Pneumonitis After RadiotherapyBonanno Laura, Pavan Alberto, Attili Ilaria, Pasello Giulia, Guarneri ValentinaJournal of Thoracic Oncology10.34
Update on tumor-infiltrating lymphocytes (TILs) in breast cancer, including recommendations to assess TILs in residual disease after neoadjuvant therapy and in carcinoma in situ A report of the International Immuno-Oncology Biomarker Working Group on Breast CancerDieci Maria Vittoria, Radosevic-Robin Nina, Fineberg Susan, van den Eynden Gert, Ternes Nils, Penault-Llorca Frederique, Pruneri Giancarlo, D'Alfonso Timothy M, Demaria Sandra, Castaneda Carlos, Sanchez Joselyn, Badve Sunil, Michiels Stefan, Bossuyt Veerle, Rojo Federico, Singh Baljit, Nielsen Torsten, Viale Giuseppe, Kim Seong-Rim, Hewitt Stephen, Wienert Stephan, Loibl Sybille, Rimm David, Symmans Fraser, Denkert Carsten, Adams Sylvia, Loi Sherene, Salgado Roberto, International Immuno-Oncology Biomarker Working Group on Breast Cancer GruppoSEMINARS IN CANCER BIOLOGY10.198
BMP9 counteracts the tumorigenic and pro-angiogenic potential of glioblastomaPorc¿¿ Elena, Maule Francesca, Boso Daniele, Rampazzo Elena, Barbieri Vito, Zuccolotto Gaia, Rosato Antonio, Frasson Chiara, Viola Giampietro, Della Puppa Alessandro, Basso Giuseppe, Persano LucaCELL DEATH AND DIFFERENTIATION8
Cell-autonomous and cell non-autonomous downregulation of tumor suppressor DAB2IP by microRNA-149-3p promotes aggressiveness of cancer cellsBellazzo A., Di Minin G., Valentino E., Sicari D., Torre D., Marchionni L., Serpi F., Stadler M.B., Taverna D., Zuccolotto G., MONTAGNER ISABELLA MONIA, Rosato Antonio, Tonon F., Zennaro C., Agostinis C., Bulla R., Mano M., Del Sal G., Collavin L.CELL DEATH AND DIFFERENTIATION8
Co-delivery of RNAi and chemokine by polyarginine nanocapsules enables the modulation of myeloid-derived suppressor cellsLedo A.M., Sasso M.S., Bronte V., Marigo Ilaria, Boyd B.J., Garcia-Fuentes M., Alonso M.J.JOURNAL OF CONTROLLED RELEASE7.877
Protamine nanocapsules as carriers for oral peptide deliveryThwala Lungile Nomcebo, Delgado Diego Pan, Leone Kevin, Marigo Ilaria, Benetti Federico, Chenlo Miguel, Alvarez Clara V, Tovar Sulay, Dieguez Carlos, Csaba Noemi Stefania, Alonso Maria JoseJOURNAL OF CONTROLLED RELEASE7.877
The role of immune microenvironment in small-cell lung cancer Distribution of PD-L1 expression and prognostic role of FOXP3-positive tumour infiltrating lymphocytesBonanno Laura, Pavan A, Dieci Maria Vittoria, Elisabetta Di Liso, Schiavon M, Comacchio G, Attili I, Pasello Giulia, Calabrese F, Rea F, Favaretto Adolfo Gino, Rugge M, Guarneri Valentina, Fassan M, Conte PierfrancoEUROPEAN JOURNAL OF CANCER7.191
[99mTc][Tc(N)(DASD)(PNP n)]+ (DASD = 1,4-Dioxa-8-azaspiro[4,5]decandithiocarbamate, PNP n = Bisphosphinoamine) for Myocardial Imaging Synthesis, Pharmacological and Pharmacokinetic StudiesSalvarese Nicola, Carta Davide, Marzano Cristina, Gerardi Gabriele, Melendez Alafort Laura, Bolzati CristinaJOURNAL OF MEDICINAL CHEMISTRY6.253
[Tc(N)PNP43]-Labeled RGD Peptides As New Probes for a Selective Detection of αvβ3 Integrin Synthesis, Structure-Activity and Pharmacokinetic StudiesBolzati Cristina, Salvarese Nicola, Carpanese Debora, Seraglia Roberta, Melendez Alafort Laura, Rosato Antonio, Capasso Domenica, Saviano Michele, Del Gatto Annarita, Comegna Daniela, Zaccaro LauraJOURNAL OF MEDICINAL CHEMISTRY6.253
STAT3 as a potential immunotherapy biomarker in oncogene-addicted non-small cell lung cancerAttili Ilaria, Karachaliou Niki, Bonanno Laura, Berenguer Jordi, Bracht Jillian, Codony-Servat Jordi, Codony-Servat Carles, Ito Masaoki, Rosell RafaelTherapeutic Advances in Medical Oncology6.238
Immune characterization of breast cancer metastases Prognostic implicationsDieci Maria Vittoria, Tsvetkova Vassilena, Orvieto Enrico, Piacentini Federico, Ficarra Guido, Griguolo Gaia, Miglietta Federica, Giarratano Tommaso, Omarini Claudia, Bonaguro Serena, Cappellesso Rocco, Aliberti Camillo, Vernaci Grazia, Giorgi Carlo Alberto, Faggioni Giovanni, Tasca Giulia, Conte Pierfranco, Guarneri ValentinaBREAST CANCER RESEARCH6.142

Source: IOV Scientific library