Immunology, Transplantation and Infectious diseases
Experimental Immunology
The Dellabona/Casorati lab investigates T cell responses in tumor immunosurveillance and immunotherapy, by combining a variety of approaches in pre-clinical and clinical models.
Research activity
The research topics of the Unit are:
- Deciphering the role in cancer of “non-conventional” T cells that recognize lipid antigens presented by CD1 molecules, non-polymorphic MHC-I-related molecules expressed by mature myeloid and B cells. CD1-restricted T cells are abundant, recognize bacterial-derived or cell-endogenous lipids, and are implicated in the control of infections, cancer and auto-immunity. We have shown that invariant Natural Killer T cells (iNKT), a subset of CD1d- restricted T cells displaying innate effector functions, rewire the prostate cancer microenvironment leading to cancer control. We are unraveling the mechanisms of this modulation in different solid and hematological malignancies and investigating ways to potentiate iNKT cell control of the tumor microenvironment for cancer immunotherapy. We have also identified a group of CD1c-restricted T cells that recognize a leukemia-associated lipid antigen and kill acute leukemia frequently expressing CD1c. We are investigating this T cell response in newly generated CD1c transgenic mice, and developing an “off-the-shelf” adoptive cell therapy strategy with T cells engineered with CD1c-restricted, leukemia-specific TCRs, which can be applied to all patients with CD1c+ leukemia recurrence following bone marrow transplantation.
- Investigating conventional MHC-restricted T cell responses specific for tumor- associated peptide antigens, and local immune contextures, in mediating cancer control in patients following neoadjuvant (pre-surgery) therapy. Failure to respond to this therapy is in fact a major unmet clinical need of solid tumors and this study may help stratify patients and inform novel approaches to improve clinical outcomes. We are assessing locally advanced oesophageal cancer, which is a paradigm for this clinical problem
The Unit is also part of TITAN project (Nanotechnologies for tumor immunotherapy; Cod: ARS01_00906). The main aim of the TITAN project is to make cancer immunotherapy with CAR-T safer, cheaper and easily accessible by developing: i) a fully automated platform for qualitative analysis of the sample throughout the production phase and ii) innovative strategies for the transduction of primary T cells using non-viral vectors avoiding the safety problems associated with the use of conventional viral vectors.
Consonni M, Garavaglia C, Grilli A, de Lalla C, Mancino A, Mori L, De Libero G, Montagna D, Casucci M, Serafini M, Bonini C, Häussinger D, Ciceri F, Bernardi M, Mastaglio S, Bicciato S, Dellabona P,* Casorati G.* Human T cells engineered with a leukemia lipid-specific TCR enables donor-unrestricted recognition of CD1c-expressing leukemia. Nat Commun. 2021 Aug 11;12(1):4844. doi: 10.1038/s41467-021-25223-0.
Exley MA, Dellabona P, Casorati G. Exploiting CD1-restricted T cells for clinical benefit. Mol Immunol. 2021 Apr;132:126-131. doi: 10.1016/j.molimm.2020.12.015.
Cortesi F, Delfanti G, Grilli A, Calcinotto A, Gorini F, Pucci F, Lucianò R, Grioni M, Recchia A, Benigni F, Briganti A, Salonia A, De Palma M, Bicciato S, Doglioni C, Bellone M, Casorati G*, Dellabona P*. Bimodal CD40/Fas-Dependent Crosstalk between iNKT Cells and Tumor-Associated Macrophages Impairs Prostate Cancer Progression. Cell Rep. 2018 Mar 13;22(11):3006-3020
Noviello M, Manfredi F, Ruggiero E, Perini T, Oliveira G, Cortesi F, De Simone P, Toffalori C, Gambacorta V, Greco R, Peccatori J, Casucci M, Casorati G, Dellabona P, Onozawa M, Teshima T, Griffioen M, Halkes CJM, Falkenburg JHF, Stölzel F, Altmann H, Bornhäuser M, Waterhouse M, Zeiser R, Finke J, Cieri N, Bondanza A, Vago L, Ciceri F, Bonini C. Bone marrow central memory and memory stem T-cell exhaustion in AML patients relapsing after HSCT. Nat Commun. 2019 Mar 25;10(1):1065. doi: 10.1038/s41467-019-08871-1.
Gorini F, Azzimonti L, Delfanti G, Scarfò L, Scielzo C, Bertilaccio MT, Ranghetti P, Gulino A, Doglioni C, Di Napoli A, Capri M, Franceschi C, Caligaris-Cappio F, Ghia P, Bellone M, Dellabona P*, Casorati G*, de Lalla C*. Invariant NKT cells contribute to chronic lymphocytic leukemia surveillance and prognosis. Blood. 2017 129:3440-3451.
Fedeli M, Riba M, Garcia Manteiga JM, Tian L, Viganò V, Rossetti G, Pagani M, Xiao C, Liston A, Stupka E, Cittaro D, Abrignani S, Provero P, Dellabona P*, Casorati G*. miR-17∼92 family clusters control iNKT cell ontogenesis via modulation of TGF-β signaling. Proc Natl Acad Sci U S A. 2016 113:E8286- E8295.
Mennonna D, Maccalli C, Romano MC, Garavaglia C, Capocefalo F, Bordoni R, Severgnini M, De Bellis G, Sidney J, Sette A, Gori A, Longhi R, Braga M, Ghirardelli L, Baldari L, Orsenigo E, Albarello L, Zino E, Fleischhauer K, Mazzola G, Ferrero N, Amoroso A, Casorati G*, Parmiani G*, Dellabona P*. T cell neoepitope discovery in colorectal cancer by high throughput profiling of somatic mutations in expressed genes. Gut. 2015 Dec 17.
Dellabona P*, Consonni M, de Lalla C, Casorati G*. Group 1 CD1-restricted T cells and the pathophysiological implications of self-lipid antigen recognition. Tissue Antigens. 2015 86:393-405
Lepore M, de Lalla C, Mori L, Dellabona P*, De Libero G*, Casorati G*. Targeting leukemia by CD1c-restricted T cells specific for a novel lipid antigen. Oncoimmunology. 2014 Dec 3;4(3):
Lepore M, de Lalla C, Gundimeda SR, Gsellinger H, Consonni M, Garavaglia C, Sansano S, Piccolo F, Scelfo A, Häussinger D, Montagna D, Locatelli F, Bonini C, Bondanza A, Forcina A, Li Z, Ni G, Ciceri F, Jenö P, Xia C, Mori L*, Dellabona P*, Casorati G*, De Libero G*. A novel self-lipid antigen targets human T cells against CD1c+ leukemias. J Exp Med. 2014 Jun 30;211(7):1363- 77.
Napolitano A, Pittoni P, Beaudoin L, Lehuen A, Voehringer D, MacDonald HR, Dellabona P*, Casorati G*. Functional education of invariant NKT cells by dendritic cell tuning of SHP-1 J Immunol. 2013 Apr 1;190(7):3299.
Casorati G, de Lalla C, Dellabona P. Invariant natural killer T cells reconstitution and the control of leukemia relapse in pediatric haploidentical hematopoietic stem cell transplantation. Oncoimmunology. 2012 May 1;1(3):355.
Tonti E, Fedeli M, Napolitano A, Iannacone M, von Andrian UH, Guidotti LG, Abrignani S, Casorati G*, Dellabona P*. Follicular helper NKT cells induce limited B cell responses and germinal center formation in the absence of CD4(+) T cell help. J Immunol. 2012. 188(7):3217.
de Lalla C, Rinaldi A, Montagna D, Azzimonti L, Bernardo ME, Sangalli LM, Paganoni AM, Maccario R, Di Cesare-Merlone A, Zecca M, Locatelli F, Dellabona P*, Casorati G*. Invariant NKT cell reconstitution in pediatric leukemia patients given HLA-haploidentical stem cell transplantation defines distinct CD4+ and CD4- subset dynamics and correlates with remission state. J Immunol. 2011. 186(7):4490-9.
de Lalla C, Lepore M, Piccolo FM, Rinaldi A, Scelfo A, Garavaglia C, Mori L, De Libero G, Dellabona P*, Casorati G*. High-frequency and adaptive-like dynamics of human CD1 self-reactive T cells. Eur J Immunol. 2011. 41(3):602. Highlighted for outstanding interest in Current Opinion in Immunology 2014, 26:1–6
Cristina Faccani
PhD student
Elise Ramia
Postdoc fellow
Arianna Sironi
Postgraduate fellow
Claudia de Lalla
Senior research associated
Alessandra Perini
Postgraduate fellow
Claudio Garavaglia
Technician
Maya Fedeli
Postdoc fellow
Michela Consonni
Postdoc fellow
Giuseppina Arbore
Postdoc fellow
Alessandra Mancino
Postdoc fellow
Gloria Delfanti
Postdoc fellow