FIG 7.

Model of how a Siglec-9-blocking antibody increases the cytotoxicity of Siglec-9⁺ NK cells. Left panel: Siglec-9^– cells have low cytotoxicity. Middle panel: the Siglec-9⁺ CD56^dim NK subset has high ADCC activity, possibly due to elevated expression of CD16 (FcγRIII; a mediator of ADCC activity), CD57 (maturation marker), and NKG2C (activating receptor), and reduced expression of the inhibitory receptor NKG2A, compared to Siglec-9^– CD56^dim NK cells. However, the Siglec-9 molecule itself is an inhibitory receptor which restrains the cytolytic ability of these highly cytotoxic Siglec-9⁺ CD56^dim NK cells by binding to Sialic acid on the surface of target cells. Right panel: blocking the inhibitory receptor, Siglec-9, using a blocking antibody can unleash a higher ADCC potential of the Siglec-9⁺ CD56^dim subpopulation.