Mast Cell-Dependent CD8 T-cell Recruitment Mediates Immune Surveillance of Intestinal Tumors in Apc Mice.

The presence of mast cells in some human colorectal cancers is a positive prognostic factor, but the basis for this association is incompletely understood. Here, we found that mice with a heterozygous mutation in the displayed reduced intestinal tumor burdens and increased survival in a chemokine decoy receptor, ACKR2-null background, which led to discovery of a critical role for mast cells in tumor defense. ACKR2Apc tumors showed increased infiltration of mast cells, their survival advantage was lost in mast cell-deficient ACKR2SAApc mice as the tumors grew rapidly, and adoptive transfer of mast cells restored control of tumor growth. Mast cells from ACKR2 mice showed elevated CCR2 and CCR5 expression and were also efficient in antigen presentation and activation of CD8 T cells. Mast cell-derived leukotriene B (LTB) was found to be required for CD8 T lymphocyte recruitment, as mice lacking the LTB receptor (ACKR2BLT1Apc) were highly susceptible to intestinal tumor-induced mortality. Taken together, these data demonstrate that chemokine-mediated recruitment of mast cells is essential for initiating LTB/BLT1-regulated CD8 T-cell homing and generation of effective antitumor immunity against intestinal tumors. We speculate that the pathway reported here underlies the positive prognostic significance of mast cells in selected human tumors. .