Immunology, Transplantation and Infectious diseases
Lymphocyte activation
Our goal is to gain a deeper understanding of the cellular and molecular mechanisms at the basis of adaptive T cell responses and tumor cell behavior. On one side this unit is dissecting the intracellular events controlling primary T cell activation and differentiation into memory cells, on the other we are tracing their behaviors in vivo in mouse models recapitulating human diseases. To these aims, we have developed tools allowing for the genetic engineering and for the tracing of antigen and tumor-specific T cells in physiological and pathological conditions.
Research activity
Current efforts are focused on two distinct and yet interconnected lines of research.
The first relates to the characterization of the role of mTOR, STAT3 and Sin3A in primary lymphocyte differentiation and in transformed cell behavior.
The second aims at validating novel adoptive T cell therapies based on the combination of engineered T cells with tumor-stroma targeting strategies, epigenetic drugs or local fractionated radiotherapy for the cure of solid tumors.
PhD Program
Please refer to the PhD studentships section in UniSR website for further details on how to apply. We offer PhD positions in two curricula:
De Beck L., Awad R.M., Basso V., Casares N., De Ridder K., De Vlaeminck Y., Gnata A., Goyvaerts C., Lecocq Q., San José-Enériz E., Verhulst S., Maes K., Vanderkerken K., Agirre X., Prosper F., Lasarte J.J*, Mondino A. J*, and Breakpot K. J*. Inhibiting histone and DNA methylation improves cancer vaccination in an experimental model of melanoma. Frontiers in Immunology. (*co-last). In Press. 2022
Pocaterra A., M. Catucci and A. Mondino. Adoptive T cell therapy of solid tumors: time to team up with immunogenic chemo/radiotherapy Current Opinion in Immunology. 74: 53-59, 2022. DOI: 10.1016/j.coi.2021.10.004
Manfredi F., D. Abbati, B.C, Cianciotti, L. Stasi, A. Potenza, E. Ruggiero, Z. Magnani, E. Carnevale, M. Doglio, M. Noviello, E. Tassi, C. Balestrieri, S. Buonanno, F. Clemente, C. De Lalla, M.P. Protti, A. Mondino, G. Casorati, P. Dellabona, and C. Bonini. Flow cytometry data mining by cytoChain identifies determinants of exhaustion and stemness in TCR-engineered T cells. Eur J Immunol. 2021 Jun 3. doi: 10.1002/eji.202049103. Online ahead of print.
Corti, A., A.Sacchi, A.M. Gasparri, M. Monieri, G. Anderluzzi, B. Colombo, A. Gori, A. Mondino, F. Curnis. Enhancement of Doxorubicin Anti-Cancer Activity by Vascular Targeting using IsoDGR/cytokine-coated Nanogold. Journal of Nanobiotechnology. 2021 May 5;19(1):128. doi: 10.1186/s12951-021-00871-y.
Mezzapelle R., F. De Marchis, C. Passera, M. Leo, F. Brambilla, F. Colombo, M. Casalgrandi, A. Preti, S. Zambrano, P. Castellani, R. Ertassi, M. Silingardi, F. Caprioglio, V. Basso, R. Boldorini, A. Carretta, F. Sanvito, O. Rena, A. Rubartelli, L.Sabatino, A. Mondino, M.P. Crippa, V. Colantuoni, and M.E. Bianchi. CXCR4 engagement triggers CD47 internalization and antitumor immunization in a mouse model of mesothelioma. EMBO Mol Med. 2021 Jun 7;13(6):e12344. doi: 10.15252/emmm.202012344. Epub 2021 May 6.
Germano G., S. Lu, G. Rospo, S. Lamba, B. Rousseau, S. Fanelli, D. Stenech, D. Le, J. Hays, M. Totaro, V. Amodio, R. Chilà, A. Mondino, L. Diaz Junior, F. Di Nicolantonio, and A. Bardelli. CD4 T cell dependent rejection of beta 2 microglobulin null mismatch repair deficient tumors. Cancer Discov. 2021 Mar 2. doi: 10.1158/2159-8290.CD-20-0987.
Vokali E., S. Yu, S. Hirosue, M. Rincon-Restrepo, F. Duraes, S. Scherer, P. Corthésy-Henrioud, W. Kilarski, A. Mondino, D. Zehn, S. Hugues, and M. Swartz. Lymphatic endothelial cells prime naïve CD8+ T cells into memory cells under steady-state conditions Nature Communications (2020)11:538 |https://doi.org/10.1038/s41467-019-14127-
Gasparri AM, Sacchi A, Basso V, Cortesi F, Freschi M, Rrapaj E, Bellone M, Casorati G, Dellabona P, Mondino A, Corti A, Curnis F. Boosting Interleukin-12 Antitumor Activity and Synergism with Immunotherapy by Targeted Delivery with isoDGR-Tagged Nanogold. Small. 2019 Sep 16:e1903462. doi: 10.1002/smll.201903462.
Gambi G., E. Di Simone, V. Basso, L. Ricci, R.Wang, A. Verma, O. Elemento, M. Ponzoni, G. Inghirami, L. Icardi* and A. Mondino*. The transcriptional regulator Sin3A contributes to the oncogenic potential of STAT3. Cancer Res. 2019 Jun 15;79(12):3076-3087. doi: 10.1158/0008-5472.CAN-18-0359. Epub 2019 Jan 28. (*co-last).
Terrazzini N., P. Mantegani, F. Kern, C. Fortis, A. Mondino* and S. Caserta*. IL-7 unveils pathogen-specific T cells by enhancing antigen-recall responses. Journal of Infectious Diseases. 2018 May 25;217(12):1997-2007. doi: 10.1093/infdis/jiy096. (*co-last).
Elia A.R., M. Grioni, V. Basso, F. Curnis, M. Freschi, A. Corti,* A. Mondino,* and M. Bellone*. Targeting tumor vasculature with TNF leads effector T cells to the tumor and enhances therapeutic efficacy of immune checkpoint blockers in combination with adoptive cell therapy. Clinical Cancer Research, 2018 2018 May 1;24(9):2171-2181. doi: 10.1158/1078-0432.CCR-17-2210. Epub 2018 Feb 28. (*co-last).
Manzo T., T. Sturmheit, V. Basso, E. Petrozziello, R. Hess Michelini, M. Riba, M. Freschi, A.R. Elia, M. Grioni, F. Curnis, M. P. Protti, T. N. Schumacher, R. Debets, M. A. Swartz, A. Corti, M. Bellone, and A. Mondino. T cells redirected to a minor histocompatibility antigen instruct intratumoral TNF-α expression and empower adoptive cell therapy for solid tumors. Cancer Res. 2017 Feb 1;77(3):658-671. doi: 10.1158/0008-5472.CAN-16-0725.
Hess Michelini, R., Manzo, T., Sturmheit, T., Basso, V., Rocchi, M., Freschi, M., Listopad, J., Blankenstein, T., Bellone, M., and A. Mondino. Vaccine-instructed intratumoral IFN-γ enables regression of autochthonous mouse prostate cancer in allogeneic T cell transplantation. Cancer Res. 2013 Aug 1;73(15):4641-52. doi: 10.1158/0008-5472.CAN-12-3464. Epub 2013 Jun 7.
Manzo T, Hess Michelini R., Basso V., Ricupito A., Chai J-C., Simpson E., Bellone M. * and A. Mondino*. (* co-last). Concurrent allo-recognition has a limited impact on post-transplant vaccination. J. Immunol. 2011 Feb 1;186(3):1361-8.
Hess Michelini R., Freschi M., Manzo T., Jachetti E., Degl’Innocenti E., Grioni M., Basso M., Bonini C., Simpson E., Mondino A.* and M. Bellone*. (* co-last) Concomitant tumor and minor histocompatibility antigen-specific immunity initiate rejection and maintain remission from established spontaneous solid tumors. Cancer Res. 2010 May 1;70(9):3505-14. Epub 2010 Apr 13.