Immunomodulation of monocyte-derived dendrite cells through ligation of tumor-produced mucins to Siglec-9

Dendritic cells (DCs) play an essential role in the induction and maintenance of an effective immune response and express multiple siglecs In the present study we investigated whether or not the ligation of tumor-produced mucins with Siglec-9 expressed on immature DCs is related to escape from immuno-surveillance in the tumor-bearing state Expression of Siglec-9 was up-regulated on the development of monocytes into immature DCs and was decreased in mature DCs Binding of various mucins and artificial glycopolymers carrying poly (NeuAc alpha 2 6 LacNAc) or poly (NeuAc alpha 2 3 LacNAc) to Siglec-9 was demonstrated by means of a plate assay These mucins also bound to the surface of immature DCs When immature DCs were treated with LPS in the presence of these mucins or artificial glycopolymers the production of IL-12 was significantly reduced but that of IL-10 was not Furthermore IL-12 production was decreased to a similar level on treatment with anti-Siglec-9 mAb Mucins prepared from serum of cancer patients actually could bind to Siglec-9 These results suggest that Siglec-9 expressed on DCs is involved in immunoregulation through ligation with mucins in an epithelial cancer patient (C) 2010 Elsevier Inc All rights reserved