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

Glycans play a crucial role in modulating cellular interactions and disease progression. In the colon, glycans serve as key mediators between host cells, the microbiome and the immune system. Yet, during tumorigenesis, glycans undergo significant alterations which influence oncogenic pathways, and, in turn, the modulated cell signalling also affects glycosylation pathways. These vicious loops contribute to several hallmarks of cancer, including sustaining proliferative signalling and immune escape, which contribute to disease progression. Increased sialylation, i.e. sialic acid-containing glycans, is typically observed in colon cancer and plays a critical role in its development, progression and poor prognosis. Truncated O-glycan structures, including the Sialyl-Tn (STn) antigen, are rarely expressed in healthy colon tissue and 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 interplay that, when imbalanced, contributes to cancer progression. This mini-review highlights the role of sialylated cancer-associated glycans in the colon, emphasising their role in cancer progression, metastasis, and interactions with the gut microbiome. Furthermore, it highlights the emerging therapeutic strategies targeting these glycans.