Engagement of sialylated glycans with Siglec receptors on myeloid suppressor cells inhibit anti-cancer immunity via CCL2

Overexpression of sialic acids on glycans, called hypersialylation is a common alteration found in cancer. Hypersialylation can, for example, enhance immune evasion via interaction with sialic acid-binding immunoglobulin-like lectin (Siglec) receptors on tumor-infiltrating immune cells. Here, we tested the role of sialic acid on myeloid-derived suppressor cells (MDSCs) and their interaction with Siglec receptors. We found that MDSCs derived from the blood of lung cancer patients and tumor-bearing mice strongly express inhibitory Siglec receptors. In murine cancer models of emergency myelopoiesis, Siglec-E knockout on myeloid cells resulted in prolonged survival and increased infiltration of activated T cells. Targeting suppressive myeloid cells by blocking Siglec receptors or desialylation led to strong reduction of their suppressive potential. We further identified CCL2 as mediator involved in T cell suppression upon interaction of sialoglycans and Siglec receptors on MDSCs. Our results provide mechanistic insights how sialylated glycans inhibit anti-cancer immunity by facilitating CCL2 expression. O_FIG O_LINKSMALLFIG WIDTH=142 HEIGHT=200 SRC="FIGDIR/small/547025v1_ufig1.gif" ALT="Figure 1"> View larger version (42K): org.highwire.dtl.DTLVardef@e7664forg.highwire.dtl.DTLVardef@1edd220org.highwire.dtl.DTLVardef@7e630dorg.highwire.dtl.DTLVardef@198ff40_HPS_FORMAT_FIGEXP M_FIG C_FIG