Viewing Siglecs through the lens of tumor immunology

Abstract

Many Siglecs function as inhibitory receptors on innate and adaptive immune cells and may contribute to the attenuation of immune responses to tumors. Siglec 9 on neutrophils and Siglec 7 on NK cells are prominent examples of inhibitory Siglecs that can potentially dampen anti-tumor immunity. CD169 is a Siglec that may function as an adhesion molecule and a facilitator of the recognition and internalization of sialic acid decorated apoptotic bodies and exosomes derived from tumors. It can potentially contribute to both the attenuation as well as the facilitation of anti-tumor immunity. Siglecs have been best studied in the tumor context in animal models of cancer. Modulators of Siglec function are likely to be developed and investigated clinically in a cancer context over the next few years.

Keywords: Siglec; cancer/tumor immunology; hypersialylation; immune evasion; immune regulation; inhibitory receptor; sialic acid.

FIGURE 1

The chemical structure of neuraminic acid, Neu5Ac, and Neu5Gc. Based on figure 1 in Schauer (2009). This figure details the various sites at which chemical alterations can be made to sialic acid that are relevant to recognition by Siglecs

FIGURE 2

Interaction of sialic acid on tumor cells with Siglec-9 on neutrophils may result in the inhibition of signaling and reduced ROS production

FIGURE 3

Interaction of sialic acid ligands on tumors cells and Siglec-7 on NK cells may dampen NK cell activation in the tumor context

FIGURE 4

CD169 on subcapsular sinus macrophages prevents tumor derived exosomes decorated with sialic acid from accessing B cells that make pro-tumorigenic antibodies and possibly from accessing naive CD8⁺ T cells as well