Mast cells boost myeloid-derived suppressor cell activity and contribute to the development of tumor-favoring microenvironment

Claudio Tripodo, Carla Guarnotta, Alice Rigoni, Francesca Mion, Luca Danelli, Stefania Marzinotto, Barbara Frossi, Laura Mariuzzi, Giorgia Gri, Carlo E. Pucillo, Ulrich Blank, Mario P. Colombo, Lucia Bongiovanni

Risultato della ricerca: Article

30 Citazioni (Scopus)

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+Grl+ 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 IFNg 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.
Lingua originaleEnglish
pagine (da-a)85-95
Numero di pagine11
RivistaCancer immunology research
Volume3
Stato di pubblicazionePublished - 2015

All Science Journal Classification (ASJC) codes

  • Immunology
  • Cancer Research

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