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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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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