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.
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.
Cortesi F, Delfanti G, Casorati G, Dellabona P. The Pathophysiological Relevance of the iNKT Cell/Mononuclear Phagocyte Crosstalk in Tissues. Front Immunol. 2018 Oct 12;9:2375.
Consonni M, Dellabona P, Casorati G. Potential advantages of CD1-restricted T cell immunotherapy in cancer. Mol Immunol. 2018 Nov;103:200-208
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
Consonni M, de Lalla C, Bigi A, Dellabona P*, Casorati G*. Harnessing the CD1 restricted T cell response for leukemia adoptive immunotherapy. Cytokine Growth Factor Rev. 2017 36:117-123.
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.
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. 2017 66:454-463.
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.
de Candia P, Torri A, Fedeli M, Viganò V, Carpi D, Gorletta T, Casorati G, Pagani M, Dellabona P, Abrignani S. The circulating microRNome demonstrates distinct lymphocyte subset-dependent signatures. Eur J Immunol. 2016 46:725- 31
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
Trajanoski Z, Maccalli C, Mennonna D, Casorati G, Parmiani G, Dellabona P. Somatically mutated tumor antigens in the quest for a more efficacious patient- oriented immunotherapy of cancer. Cancer Immunol Immunother. 2015 Jan;64(1):99-104.
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.
Dellabona P*, Abrignani S*, Casorati G*. iNKT-cell help to B cells: A cooperative job between innate and adaptive immune responses. Eur J Immunol. 2014 Aug;44(8):2230-7.