title: Mast cells boost myeloid-derived suppressor cell activity and contribute to the development of tumor-favoring microenvironment.
abstract: Inflammation plays crucial roles at different stages of tumor development and may lead to the failure of immune surveillance and immunotherapy. Myeloid-derived suppressor cells (MDSC) are one of the major components of the immune-suppressive network that favors tumor growth, and their interaction with mast cells is emerging as critical for the outcome of the tumor-associated immune response. Herein, we showed the occurrence of cell-to-cell interactions between MDSCs and mast cells in the mucosa of patients with colon carcinoma and in the colon and spleen of tumor-bearing mice. Furthermore, we demonstrated that the CT-26 colon cancer cells induced the accumulation of CD11b(+)Gr1(+) immature MDSCs and the recruitment of protumoral mast cells at the tumor site. Using ex vivo analyses, we showed that mast cells have the ability to increase the suppressive properties of spleen-derived monocytic MDSCs, through a mechanism involving IFNγ and nitric oxide production. In addition, we demonstrated that the CD40:CD40L cross-talk between the two cell populations is responsible for the instauration of a proinflammatory microenvironment and for the increase in the production of mediators that can further support MDSC mobilization and tumor growth. In light of these results, interfering with the MDSC:mast cell axis could be a promising approach to abrogate MDSC-related immune suppression and to improve the antitumor immune response.
authors.affiliation: Department of Medical and Biological Science, University of Udine, Udine, Italy. Inserm UMRS-1149; CNRS ERL 8252; Université Paris Diderot, Sorbonne Paris Cite, Laboratoire d'excellence INFLAMEX, 75018 Paris, France.
authors.forename: Luca
authors.initials: L
authors.lastname: Danelli
authors.affiliation: Department of Medical and Biological Science, University of Udine, Udine, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Frossi
authors.affiliation: Department of Medical and Biological Science, University of Udine, Udine, Italy.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Gri
authors.affiliation: Department of Medical and Biological Science, University of Udine, Udine, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Mion
authors.affiliation: Department of Health Science, University of Palermo, Palermo, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Guarnotta
authors.affiliation: Department of Health Science, University of Palermo, Palermo, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Bongiovanni
authors.affiliation: Department of Health Science, University of Palermo, Palermo, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Tripodo
authors.affiliation: Department of Medical and Biological Science, University of Udine, Udine, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Mariuzzi
authors.affiliation: Department of Medical and Biological Science, University of Udine, Udine, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Marzinotto
authors.affiliation: Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Alice
authors.initials: A
authors.lastname: Rigoni
authors.affiliation: Inserm UMRS-1149; CNRS ERL 8252; Université Paris Diderot, Sorbonne Paris Cite, Laboratoire d'excellence INFLAMEX, 75018 Paris, France.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Blank
authors.affiliation: Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy. carlo.pucillo@uniud.it mariopaolo.colombo@istitutotumori.mi.it.
authors.forename: Mario P
authors.initials: MP
authors.lastname: Colombo
authors.affiliation: Department of Medical and Biological Science, University of Udine, Udine, Italy. carlo.pucillo@uniud.it mariopaolo.colombo@istitutotumori.mi.it.
authors.forename: Carlo E
authors.initials: CE
authors.lastname: Pucillo
mesh_terms: D000818:Animals; D019013:CD40 Antigens / Q000378:metabolism; D023201:CD40 Ligand / Q000378:metabolism; D002450:Cell Communication; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000628:therapy*; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D007371:Interferon-gamma / Q000276:immunology; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000276:immunology*; D009569:Nitric Oxide / Q000378:metabolism; D059016:Tumor Microenvironment / Q000276:immunology*
chemical_list: D019013:CD40 Antigens; D023201:CD40 Ligand; D009569:Nitric Oxide; D007371:Interferon-gamma