N-Glycans as fundamental immune-checkpoints at the frontiers of inflammation, autoimmunity and cancer

Abstract

Glycans cover the surface of essentially all cells, giving rise to the so-called glycocalyx. Glycans, and particularly N-glycans are key players in defining the fate and the nature of the immune response, participating in both pro-inflammatory and anti-inflammatory pathways occurring in inflammation, autoimmunity and cancer. Glycans and glycan-binding proteins (GBPs) are instrumental molecules that integrate the immunological landscape in homeostasis, being involved in how the host immune system perceives the self and non-self. Perturbations in these immune regulatory circuits created by glycans and GBPs may result in the loss of immune tolerance associated with autoimmunity and inflammatory conditions, but also in malignant transformation. This chapter will discuss the regulatory role played by N-glycans as fundamental immune-checkpoints in the interplay between the immune cells and their surrounding microenvironment associated with homeostasis and disease. Furthermore, we will also explore how N-glycans can act as promising diagnostic and prognostic biomarkers in disease, as well as appealing targets for new therapeutic approaches in inflammation, autoimmunity and cancer.