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Review
. 2017 Mar;276(1):178-191.
doi: 10.1111/imr.12526.

Viewing Siglecs through the lens of tumor immunology

Isabella Fraschilla  1 , Shiv Pillai  1
Affiliations
Review

Viewing Siglecs through the lens of tumor immunology

Isabella Fraschilla et al. Immunol Rev. 2017 Mar.

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.

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Conflict of interest statement

CONFLICT OF INTEREST

The authors have no conflicts of interest.

Figures

FIGURE 1
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
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
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
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
See this image and copyright information in PMC

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