Glycans as shapers of tumour microenvironment: A sweet driver of T-cell-mediated anti-tumour immune response.

Essentially all cells are covered with a dense coat of different glycan structures/sugar chains, giving rise to the so-called glycocalyx. Changes in cellular glycosylation are a hallmark of cancer, affecting most of the pathophysiological processes associated with malignant transformation, including tumour immune responses. Glycans are chief macromolecules that define T-cell development, differentiation, fate, activation and signalling. Thus, the diversity of glycans expressed at the surface of T cells constitutes a fundamental molecular interface with the microenvironment by regulating the bilateral interactions between T-cells and cancer cells, fine-tuning the anti-tumour immune response. In this review, we will introduce the power of glycans as orchestrators of T-cell-mediated immune response in physiological conditions and in cancer. We discuss how glycans modulate the glyco-metabolic landscape in the tumour microenvironment, and whether glycans can synergize with immunotherapy as a way of rewiring T-cell effector functions against cancer cells.

Glycans as a key factor in self and nonself discrimination: impact on the breach of immune tolerance.

Glycans are carbohydrates that are made by all organisms and covalently conjugated to other biomolecules. Glycans cover the surface of both human cells and pathogens and are fundamental to defining the identity of a cell or an organism, thereby contributing to discriminating self from nonself. As such, glycans are a class of 'Self-Associated Molecular Patterns' that can fine-tune host inflammatory processes. In fact, glycans can be sensed and recognized by a variety of glycan-binding proteins (GBP) expressed by immune cells, such as galectins, siglecs, and C-type lectins, which recognize changes in the cellular glycosylation, instructing both pro-inflammatory and anti-inflammatory responses. In this review, we introduce glycans as cell-identification structures, discussing how glycans modulate host-pathogen interactions and how they can fine-tune inflammatory processes associated with infection, inflammation and autoimmunity. Finally, from the clinical standpoint, we discuss how glycoscience research can benefit life sciences and clinical medicine by providing a source of valuable biomarkers and therapeutic targets for immunity.

Bringing to Light the Risk of Colorectal Cancer in Inflammatory Bowel Disease: Mucosal Glycosylation as a Key Player.

Colitis-associated cancer is a major complication of inflammatory bowel disease remaining an important clinical challenge in terms of diagnosis, screening, and prognosis. Inflammation is a driving factor both in inflammatory bowel disease and cancer, but the mechanism underlying the transition from colon inflammation to cancer remains to be defined. Dysregulation of mucosal glycosylation has been described as a key regulatory mechanism associated both with colon inflammation and colorectal cancer development. In this review, we discuss the major molecular mechanisms of colitis-associated cancer pathogenesis, highlighting the role of glycans expressed at gut epithelial cells, at lamina propria T cells, and in serum proteins in the regulation of intestinal inflammation and its progression to colon cancer, further discussing its potential clinical and therapeutic applications.

Colitis-associated cancer (CAC) is a major complication of inflammatory bowel disease and the molecular mechanisms underlying CAC progression are still elusive. Protein glycosylation holds a great promise for improving the understanding of CAC immunopathogenesis, opening new avenues for clinical and therapeutic interventions.