Affordable Access

deepdyve-link
Publisher Website

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

Authors
  • Danelli, Luca
  • Frossi, Barbara
  • Gri, Giorgia
  • Mion, Francesca
  • Guarnotta, Carla
  • Bongiovanni, Lucia
  • Tripodo, Claudio
  • Mariuzzi, Laura
  • Marzinotto, Stefania
  • Rigoni, Alice
  • Blank, Ulrich
  • Colombo, Mario P
  • Pucillo, Carlo E
Type
Published Article
Journal
Cancer Immunology Research
Publisher
American Association for Cancer Research
Publication Date
Jan 01, 2015
Volume
3
Issue
1
Pages
85–95
Identifiers
DOI: 10.1158/2326-6066.CIR-14-0102
PMID: 25351848
Source
Medline
License
Unknown

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.

Report this publication

Statistics

Seen <100 times