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RESEARCH PRODUCT
Mast cells boost myeloid-derived suppressor cell activity and contribute to the development of tumor-favoring microenvironment
Claudio TripodoMario P. ColomboUlrich BlankLuca DanelliCarlo PucilloStefania MarzinottoGiorgia GriFrancesca MionLucia BongiovanniLaura MariuzziAlice RigoniBarbara FrossiCarla Guarnottasubject
Cancer Researchmedicine.medical_treatmentCD40 LigandImmunologyInflammationCell CommunicationBiologyNitric OxideProinflammatory cytokineInterferon-gammaMiceImmune systemAntigens CD40Animals; Antigens CD40; CD40 Ligand; Cell Line Tumor; Colonic Neoplasms; Humans; Inflammation; Interferon-gamma; Mast Cells; Mice; Mice Inbred BALB C; Mice Knockout; Myeloid Cells; Nitric Oxide; Tumor Microenvironment; Cell Communication; Cancer Research; Immunology; Medicine (all)Cell Line TumormedicineMast cell; Myeloid-Derived Suppressor Cell; tumor microenvironment; colon cancerTumor MicroenvironmentAnimalsHumansMyeloid-Derived Suppressor CellMast CellMyeloid CellsMast CellsCD40 AntigensMyeloid CellInflammationMice KnockoutTumor microenvironmentColonic NeoplasmMice Inbred BALB CCD40AnimalMedicine (all)ImmunotherapyMast cellmedicine.anatomical_structurecolon cancerImmunologyColonic NeoplasmsCancer researchMyeloid-derived Suppressor Cellbiology.proteinmedicine.symptomHumandescription
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. Cancer Immunol Res; 3(1); 85–95. ©2014 AACR.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2014-10-30 |