Mast cells and mast cell-derived IL-13 play an important role in MDSC activation, migration, and accumulation. (TUM4P.925)

Abstract

Until recently, the interaction between mast cells (MCs) and CD11b+Gr-1+ myeloid derived suppressor cells (MDSCs) was limited to recruitment of MDSCs to the tumor site. However, we report that MCs are also needed for the activity of MDSCs. Adoptive transfer (AT) of MDSCs failed to promote B16 melanoma colonization in MC deficient mice. MDSCs in these mice also failed to localize to the liver and stayed mainly in peripheral blood. MC sufficient mice accumulated MDSCs in the liver and retained significantly lower levels of MDSCs in circulation after AT. Recently, Ma et al. (Cancer Res. 2013 Jul 1; 73(13);3927-37.) has shown that MC derived IL-13 has been show to promote the growth of pancreatic ductal carcinoma. Given this, we investigated the role that IL-13 plays in the MDSC/MC interaction. Our data shows that IL-13 KO mice crossed to ADAM10Tg mice, which carry a mutation resulting in the over-accumulation of MDSCs, have significantly decreased MDSC accumulation in the naïve state, especially evident in the granulocytic subset. In a model of natural MDSC accumulation (Lewis Lung Carcinoma, i.v.), IL-13 KO mice had reduced tumor colonization to the lungs. They also had reduced MDSC accumulation in the liver and spleen, but increased number in circulation. Taken together, our data indicates that MCs and IL-13, an important MC-derived cytokine, play an important role in MDSC migration and accumulation and represent important drug targets for the control of MDSCs in tumor.