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 (MDSCs) are one of the major components of the immune-suppressive network that favors tumor growth, and their interaction with mast cells (MCs) 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 MCs in the mucosa of colon carcinoma patients and in the colon and spleen of tumor-bearing mice. Furthermore we demonstrate that the CT-26 colon cancer induces the accumulation of CD11b+Gr1+ immature MDSCs and the recruitment of pro-tumoral MCs at tumor site. Through ex vivo analyses we show that MCs have the ability to increase the suppressive properties of spleen-derived monocytic-MDSCs, through a mechanism involving IFN-γ and nitric oxide production. In addition, we demonstrate that the CD40:CD40L cross-talk between the two populations is responsible for the instauration of a pro-inflammatory microenvironment and for the increase in the production of mediators that can further support MDSCs mobilization and tumor growth. In light of these results, interfering with the MDSC:MC axis could be a promising approach to abrogate MDSC-related immune suppression and to improve the anti-tumor immune response.
- Received May 25, 2014.
- Revision received September 24, 2014.
- Accepted October 11, 2014.
- Copyright © 2014, American Association for Cancer Research.