Immunology: glyco-engineering 'super-self'

Abstract

Altered glycosylation of cancer cells confers phenotypic changes that promote spread and evasion of immune responses. A novel method for engineering cell surface glycans is providing insights into these mechanisms.

Figure 1. Sialic acid mediated recruitment of Siglec-7 inhibits NK cell activation

(a) Cells with low levels of sialic acid (hyposialylated) are ‘missing self’, resulting in strong activation of the NK cells (left). Glyco-engineering target cells with sialic acid polymers can transform them into ‘super self’, where the high density of ligands efficiently recruits Siglec-7 to suppress NK cell activation (right). (b) Endogenous levels of sialic acids comprise ‘self’ markers on normal cells, which may engage Siglec-7 to aid in ‘self’ recognition and suppress unwanted activation of NK cells (left). Many cancer cells have higher levels of sialic acid (hypersialylated), which could recruit more Siglec-7 and provide a strong inhibitory signal to the NK cells and help in immune evasion.