Impact of the Siglec-Sialoglycan Axis on the Cancer Immune Response

Abstract

Sialic acid-binding immunoglobulin-like lectins (Siglecs) have heavily mediated the tumour landscape and shown significant deregulation in many tumour malignancies by facilitating tumour progression and metastasis; such sialoglycan ligands have also contributed to tumour development. Primarily, the Siglec/sialoglycan axis is capable of modulating immunosuppression and signalling pathways, preventing myeloid cell activation and subsequent generation of an immune response. This book chapter highlights the multifaceted roles of the Siglec/sialoglycan axis and outlines Siglec expression, their therapeutic potential as diagnostic and prognostic biomarkers, and current murine models and techniques used to further elucidate key signalling pathways and downstream targets. Additionally, we have elaborated on the role of certain key enzymes involved in sialoglycan synthesis and the involvement of glycosylation and subsequent hypersialylation and immune modulation in the tumour microenvironment. Finally, we suggest key areas through which to further expand on the understanding of Siglec function and highlight roles in maintaining tumour heterogeneity. In addition to this, the usage of Siglec-targeting therapies may also enhance or optimise current immunotherapeutic interventions upon further experimental validation.