Cancer-associated O-glycans and microbiome interactions in colorectal cancer: insights into tumor progression and immune evasion

Abstract

Glycans play a crucial role in modulating cellular interactions and disease progression. In the colon, they serve as key mediators between host cells, the microbiome, and the immune system. During tumorigenesis, however, glycans undergo significant alterations that not only influence oncogenic pathways but are also affected by changes in cell signaling, creating a self-perpetuating cycle. These feedback loops drive several cancer hallmarks, including sustained proliferative signaling and immune escape, thereby promoting disease progression. One prominent alteration in colorectal cancer is increased sialylation - the enrichment of sialic acid-containing glycans - which is strongly linked to tumor development, progression, and poor prognosis. Truncated O-glycan structures, such as the Sialyl-Tn (STn) antigen, are rarely presented in healthy colon tissue but are commonly associated with oncogenic transformation and immune evasion. Both commensal and pathogenic bacteria in the colon exploit host sialylated glycans as adhesion sites and nutrient sources. This interaction modulates local immune responses and inflammation, contributing to a complex and dynamic interplay that, when disrupted, accelerates cancer progression. This mini-review discusses the role of sialylated cancer-associated glycans in colorectal cancer, emphasising their involvement in tumor progression, metastasis, and interactions with the gut microbiome. Furthermore, it highlights emerging therapeutic strategies that target these glycans.