Differential migration of myeloid-derived suppressor cell subsets to tumor-draining lymph nodes in a murine model of breast cancer (P2014)

Abstract

Abstract Myeloid-derived suppressor cells (MDSC) expand in cancer and suppress the anti-tumor immune response. MDSC are morphologically and functionally divided into monocytic (MO-MDSC) and polymorphonuclear (PMN-MDSC) subsets, identified as CD11b+Ly-6G-Ly-6Chigh and CD11b+Ly-6G+Ly-6Clow, respectively. MDSC accumulate primarily in the blood and spleen, but their suppressive function is limited to the tumor and tumor-draining lymph nodes (TDLN). We sought to determine the involvement of adhesion molecules in MDSC migration to TDLN using the 4T1 murine breast cancer model. Both MDSC subsets expressed L-selectin and LFA-1, although L-selectin levels were higher on MO-MDSC. To determine whether this differential L-selectin expression affected MDSC migration to TDLN, we analyzed tissue distribution and in vivo migration of wild type and L-selectin-deficient MDSC. In the blood and spleen of wild type mice, the PMN-MDSC subset predominated (MO-MDSC/PMN-MDSC ratio of 0.1), while the MO-MDSC subset predominated in the TDLN (ratio of 1.5). By contrast, in L-selectin-deficient mice, the MO-MDSC/PMN-MDSC ratios in the TDLN (0.3) and in the blood and spleen (0.1) were similar. This differential tissue distribution was consistent with increased TDLN entry of wild type, but not L-selectin-deficient, MO-MDSC relative to PMN-MDSC in adoptive transfer experiments. Taken together, these results suggest a migratory preference of MO-MDSC to the TDLN dependent on L-selectin.