Siglecs: targets for immune regulation and cancer therapy

Siglecs (sialic acid-binding immunoglobulin-type lectins) are receptors predominantly located on the surface of hematopoietic cells. Recent publications highlight the important roles Siglecs play in tumor immunosurveillance making them attractive anti-cancer drug targets. Inhibitory receptors Siglec-7 and Siglec-9 are expressed on NK cells and recognize tumor-associated sialosides (1,2). Also, Siglec-15 (Catalog # 9227-SL) was identified as an immune suppressor by engaging an unknown receptor on T cells. Similar to PD-L1/PD-1 immune checkpoint blockade, Siglec-15 may be a potential target for cancer immunotherapy (3).

Siglecs interact with an array of linkage-specific sialic acids on a glycan structure expressed on host cells, as well as pathogens. So far, there are 15 different human and 9 murine Siglecs. Each type of Siglec generally recognizes a particular set of sialylated glycan containing differently linked sialic acid molecules (4,5). On the cytoplasmic side, most Siglecs have immune receptor tyrosine-based inhibition motifs (ITIM), which initiate signaling cascades resulting in downregulation of proinflammatory responses.

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Protein	Species	Source	Tag	Catalog #	Activity
Siglec-1/CD169	Human	NS0	His	A5197-SL	Supports RBC adhesion
	Mouse	NS0	Fc	5610-SL
Siglec-2/CD22	Human	NS0	Fc	1968-SL	Supports RBC adhesion
	Mouse	NS0	Fc	2296-SL
	Cyno	HEK293	His	9864-SL
	Cyno	HEK293	Fc	10031-SL
Siglec-3/CD33	Human	NS0	Fc	1137-SL	Supports RBC adhesion
Siglec-4a/MAG	Human	HEK293	Fc	8940-MG	Inhibits neurite outgrowth of E13 chick embryonic DRG neurons
	Mouse	NS0	Fc	8580-MG
	Rat	NS0	Fc	538-MG
Siglec-5/CD170	Human	NS0	Fc	1072-SL	Supports RBC adhesion
Siglec-6/CD327	Human	CHO	Fc	2859-SL	Binds biotinylated Neu5Ac alpha 2-6GalNAc alpha
Siglec-7/CD328	Human	NS0	Fc	1138-SL	Supports RBC adhesion
Siglec-8	Human	NS0	Fc	9045-SL	Binds biotinylated Sialyl Lewis X
Siglec-9	Human	NS0	Fc	1139-SL	Supports RBC adhesion
Siglec-10	Human	NS0	Fc	2130-SL	Binds biotinylated 6’-Sialyllactose-Polyacrylamide
Siglec-11	Human	CHO	Fc	3258-SL	Binds biotinylated (Neu5Aca2-8)2-Polyacrylamide
Siglec-14	Human	NS0	Fc	4905-SL	Supports RBC adhesion
Siglec-15	Human	CHO	Fc	9227-SL	Inhibits anti-CD3 induced IFN-gamma secretion by T cells
Siglec-E	Mouse	NS0	Fc	5806-SL	Binds biotinylated Neu5Ac alpha 2-6GalNAc alpha -Polyacrylamide
Siglec-F	Mouse	NS0	Fc	1706-SF	Supports RBC adhesion
	Mouse	NS0	His	10171-SF New!
Siglec-G	Mouse	NS0	Fc	10103-SL New!	Binds biotinylated 6'-Sialylactose-PAA

References:

1. Jandus, C. et al. (2014) J. Clin. Investig. 124:1810.

2. Stanczak, M.A. et al. (2018) J. Clin. Investig. 128:4912.

3. Wang, J. et al. (2019) Nat. Med. 25:656.

4. Bornhöfft, K.F. et al. (2018) Dev. Comp. Immunol. 86:219.

5. Zhou, J.Y. et al. (2018) Trends Immunol. 39:523.

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