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 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