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.
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, Caputo S, Bellone M. Immune CheckpointMediated Interactions Between Cancer and Immune Cells in Prostate Adenocarcinoma and Melanoma. Front Immunol. 2018 Jul 31;9:1786. d
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.
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.
Bellone M, Elia AR. Constitutive and acquired mechanisms of resistance to immune checkpoint blockade in human cancer. Cytokine Growth Factor Rev. 2017 Aug;36:17-24.
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.
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, CaligarisCappio 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 Jun 29;129(26):3440-3451.
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.
Calcinotto A, Ponzoni M, Ria R, Grioni M, Cattaneo E, Villa I, Bertilaccio MTS, Chesi M, Rubinacci A, Tonon G, Bergsagel LP, Vacca A, Bellone M. Modifications of the mouse bone marrow microenvironment favor angiogenesis and correlate with disease progression from asymptomatic to symptomatic multiple myeloma. Oncoimmunology 2015 May 7;4(6):e1008850.
Parmiani G, Pilla L, Corti A, Doglioni C, Cimminiello C, Bellone M, Parolini D, Russo V, Capocefalo F, Maccalli C. A pilot phase I study combining peptide-based vaccination and NGR-hTNF vessel targeting therapy in metastatic melanoma. Oncoimmunology 2014 Dec 21;3(11):e963406.
Jachetti E, Mazzoleni S, Grioni M, Ricupito A, Brambillasca C, Generoso L, Calcinotto A, Freschi M, Mondino A, Galli R, Bellone M. Prostate cancer stem cells are targets of both innate and adaptive immunity and elicit tumor-specific immune responses. Oncoimmunology. 2013 May 1;2(5):e24520.
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.