The immune system is made of cells and soluble factors, whose main function is to identify and fight what might be dangerous for the organism (e.g., virus, bacteria, exogenous proteins). Thus, innate and adaptive immune responses tightly cooperate at this task with excellent results. Is a tumor regarded as dangerous by the immune system? Tumor cells possess antigens (i.e., signals detected by the cells of the immune system) that can trigger an immune response. While in vitro and in animal models tumors elicit immune responses, spontaneous rejection of measurable tumors rarely occurs in humans. Which are therefore, the rules governing the interactions among a growing tumor, its surrounding stroma and the immune system?
Major goal of this group is to achieve a deeper understanding of the molecular events regulating the interactions among transformed cells, their surrounding stroma and the immune system during the different phases of tumor development and progression. This knowledge is then implemented to identify means whereby induce in vivo a therapeutic tumor-specific immune response. Final goal is to translate the most promising among these novel therapies into clinical trials.
- Dynamic interactions between cancer stem-like cells and the immune system in prostate cancer.
- Cancer cell-immune cell interactions in the bone marrow driving tumor progression in multiple myeloma.
- Targeting the tumor microenvironment to increase the therapeutic efficacy of immunotherapy.
Pernigoni N, Zagato E, Calcinotto A, Troiani M, Mestre RP, Calì B, Attanasio G, Troisi J, Minini M, Mosole S, Revandkar A, Pasquini E, Elia AR, Bossi D, Rinaldi A, Rescigno P, Flohr P, Hunt J, Neeb A, Buroni L, Guo C, Welti J, Ferrari M, Grioni M, Gauthier J, Gharaibeh RZ, Palmisano A, Lucchini GM, D'Antonio E, Merler S, Bolis M, Grassi F, Esposito A, Bellone M, Briganti A, Rescigno M, Theurillat JP, Jobin C, Gillessen S, de Bono J, Alimonti A. Commensal bacteria promote endocrine resistance in prostate cancer through androgen biosynthesis. Science. 2021 Oct 8;374(6564):216-224. doi: 10.1126/science.abf8403. Epub 2021 Oct 7
Grioni M, Brevi A, Cattaneo E, Rovoda A, Bordini J, Bertilaccio MTS, Ponzoni M, Casorati G, Dellabona P, Ghia P, Bellone M*, Calcinotto A. CD4+ T cells sustain aggressive chronic lymphocytic leukemia in Eμ-TCL1 mice through a CD40L-independent mechanism. *Co-last and corresponding author. Blood Adv. 2021 Jul 27;5(14):2817-2828. doi: 10.1182/bloodadvances.2020003795
Bellone M*, Calcinotto A, Huber S. Microbiota-propelled T helper 17 cells in inflammatory diseases and cancer. *Corresponding author. Microbiol Mol Biol Rev. 2020 Mar 4;84(2):e00064-19. doi: 10.1128/MMBR.00064-19. Paper featured in the journal cover.
Caputo S, Grioni M, Brambillasca CS, Monno A, Brevi A, Freschi M, Piras IS, Elia AR, Pieri V, Baccega T, Lombardo A, Galli R, Briganti A, Doglioni C, Jachetti E, Bellone M. Galectin-3 in prostate cancer stem-like cells is immunosuppressive and drives early metastasis. Front Immunol. 10 September 2020
Calcinotto A, Brevi A, Chesi M, Ferrarese R, Garcia Perez L, Grioni M, Kumar S, Garbitt VM, Sharik ME, Henderson KJ, Tonon G, Tomura M, Miwa Y, Esplugues E, Flavell RA, Huber S, Canducci F, Rajkumar VS, Bergsagel PL, Bellone M. Microbiotadriven interleukin-17-producing cells and eosinophils synergize to accelerate multiple myeloma progression. Nat Commun. 2018 Dec 3;9(1):4832.
Elia AR, Grioni M, Basso V, Curnis F, Freschi M, Corti A, Mondino A, Bellone M. Targeting tumor vasculature with TNF leads effector T cells to the tumor and enhances therapeutic efficacy of immune checkpoint blockers in combination with ACT. Clin Cancer Res. 2018 Feb 28.
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.
Petitprez, F, Fossati N, Vano Y, Freschi M, Becht E, Lucianò R, Calderaro J, Guédet T, Lacroix L, Rancoita RMV, Montorsi F, Fridman WF, SautèsFridman C, Briganti A, Doglioni C, Bellone M. PD-L1 expression and CD8+ T-cell infiltrate are associated with clinical progression in patients with node-positive prostate cancer. Eur Urol Focus. 2017 Jun 21. pii: S2405-4569(17)30151-7.
Jachetti E, Caputo S, Mazzoleni S, Brambillasca CS, Parigi SM, Grioni M, Piras IS, Restuccia U, Calcinotto A, Freschi M, Bachi A, Galli R, Bellone M. Tenascin-C protects cancer stem like cells from immune surveillance by arresting T-cell activation. Cancer Res. 2015 May 15;75(10):2095108.
Hess Michelini R, Manzo T, Sturmheit T, Basso V, Rocchi M, Freschi M, Listopad J, Blankenstein T, Bellone M*, Mondino A*. 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.
Ricupito A, Grioni M, Calcinotto A, Hess Michelini R, Longhi R, Mondino A, Bellone M. Booster vaccinations against cancer are critical in prophylactic but detrimental in therapeutic settings. Cancer Res. 2013 Jun 15;73(12):3545-54.
Calcinotto A, Filipazzi P, Grioni M, Iero M, De Milito A, Ricupito A, Cova A, Canese R, Jachetti E, Rossetti M, Huber V, Parmiani G, Generoso L, Borghi M, Santinami M, Borghi M, Fais S, Bellone M*, Rivoltini L. Modulation of microenvironmental acidity reveres anergy in human and murine tumorinfiltrating T lymphocytes. Cancer Res. 2012 Jun 1;72(11):2746-56.
Calcinotto A, Grioni M, Jachetti E, Curnis F, Mondino A, Parmiani G, Corti, Bellone M. Targeting tumor necrosis factor-alpha to neoangiogenic vessels enhances lymphocyte infiltration in tumors and increases the therapeutic potential of immunotherapy. J Immunol. 2012 Mar 15;188(6):2687-94.
Rigamonti N, Capuano G, Ricupito A, Jachetti E, Grioni M, Generoso L, Freschi M, Bellone M. Modulators of arginine metabolism do not impact on peripheral T-cell tolerance and disease progression in a model of spontaneous prostate cancer. Clin Cancer Res, 2011 Mar 1;17(5):1012-23. Epub 2011 Jan 19
Michelini RH, Freschi M, Manzo T, Jachetti E, Degl’Innocenti E, Grioni M, Basso V, Bonini C, Simpson E, Mondino A* and Bellone M*. Concomitant tumor and minor histocompatibility antigen-specific immunity initiate rejection and maintain remission from established spontaneous solid tumors. Cancer Res., 2010, May 1;70:3505-14