My First AIRC grant @Tumour Immunology Unit
Tumour Immunology Unit was established with a support of the Italian Association for Cancer Research (AIRC) program called “My First AIRC grant”. This grant aims to support young researchers in establishing independent laboratories focused on the cutting-edge oncology research. My First AIRC project “Dissecting ILT3 biology to understand tumor suppression in B cell chronic lymphocytic leukemia" aims to get a deeper understanding of the mechanism ensuring that some tumours are slower in development than others and to harness this knowledge for therapy development. Specifically, we are interested in studying one of the most frequent tumours of B lymphocytes, B-cell chronic lymphocytic leukemia (CLL), which is characterized by high incidence of indolent disease suggesting that in CLL a molecular network suppressing tumour progression is in place. Our knowledge on this network and its regulation is relatively fragmentary, therefore we aim to deepen it and use it to treat aggressive B cell tumours.
Research lines
Membrane receptor dynamics regulating B cell signaling
Our laboratory combines the state-of-the-art imaging, molecular and signaling studies to understand better the dynamics of regulatory receptors expressed on B cells from CLL patients. CLL B cells bear some particular inhibitory immune receptors, such as ILT3, which undergo a dynamic redistribution upon CLL cell stimulation. In order to characterize functional significance of this process, in our project we will explore the mechanism regulating surface patterning of ILT3 and other inhibitory B cell receptors. These findings will enrich our understanding of inhibitory signaling mechanisms in B cells, both in cancer and in health.
Inhibitory gene networks in CLL and their therapeutic potential
We are particularly interested in characterizing, by a combination of proteomics, transcriptomics and gene editing approaches in vitro and in vivo, CLL-specific gene networks which inhibit B cell tumour development. Results of this study may form a rationale for the development of novel therapeutic approaches to treat aggressive CLL. Although new-generation chemotherapeutic agents and immunotherapies based on B cell- specific antibodies have revolutionized CLL treatment, about 30-40% of cases still have a poor therapeutic outcome. This project has a founded potential to guide the design of novel therapies that may improve therapeutic schedules for CLL patients who relapse post-treatment. Also, this expectation may be extended to other B cell lymphoproliferative disorders, because of the common cellular source of the tumour.
Selected Publications of the Principal Investigator (PI)
Zurli, V., Wimmer, G., Cattaneo, F., Candi, V., Cencini, E., Gozzetti, A., Raspadori, D., Campoccia, G., Sanseviero., F., Bocchia, M., Baldari, C.T., Kabanova, A. Ectopic ILT3 controls BCR- driven activation of Akt in B-cell chronic lymphocytic leukemia. Blood 130 (18):2006-2017 (2017)
Kabanova, A.*, Sanseviero, F., Candi, V., Gamberucci, A., Gozzetti, A., Campoccia, G., Bocchia, M., Baldari, C.T. Human cytotoxic T lymphocytes form dysfunctional immune synapses with B cells characterized by non-polarized lytic granule release. Cell Reports 15, 1-10 (2016)
Kabanova, A., Marcandalli, J., Zhou, T., Bianchi, S., Baxa, U., Tsybovsky, Y., Lilleri, D., Silacci- Fregni, C., Foglierini, M., Fernandez-Rodriguez, B.M., Druz, A., Zhang, B., Geiger, R., Pagani, M., Sallusto, F., Kwong, P.D., Corti, D., Lanzavecchia, A., Perez, L. Platelet-derived growth factor-α receptor is the cellular receptor for human cytomegalovirus gHgLgO trimer. Nature Microbiology pii: 16082 (2016)
Kabanova, A., Perez, L., Lilleri, D., Marcandalli, J., Agatic, G., Becattini, S., Preite, S., Fuschillo, D., Percivalle, E., Sallusto, F., Gerna, G., Corti, D., Lanzavecchia, A. Antibody-driven design of a human cytomegalovirus gHgLpUL128L subunit vaccine that selectively elicits potent neutralizing antibodies. Proc Natl Acad Sci U S A. 16;111(50):17965-70 (2014)
Referenti:
Cristina Tinti
c.tinti@toscanalifesciences.org
