Gastrointestinal cancers are among the leading causes of mortality worldwide. Malignancy susceptibility varies markedly along the gastrointestinal tract, with the stomach and colon being more prone to adenocarcinomas than the small intestine. Experimental evidence suggests that these differences are driven by regional variations in microbiota, the immune response or epithelial biology along the mucosa. 

Dysregulation of local immune cell composition, including abnormal T-cell responses, has been associated with increased risk of gastric and colorectal cancers. While the gastric immune microenvironment is characterized by a tendency toward Th2 polarization, the colon displays a predominantly Th17-driven response. These immune changes could be explained via glyco-immunology. Tissue or diseased-state differences in epithelial glycosylation can affect immune interactions, influencing the activation/inhibition of certain immune cells and polarizing the response towards cancer development.

A systematic characterization of regional glycosylation and immune landscapes in the human gastrointestinal tract is still lacking. This exploratory study aims to comprehensively map epithelial and immune cell glycosylation patterns along the human gut using spatial proteomic multiplex immunofluorescence analyses. By correlating local glycan and immune profiles, the project seeks to elucidate mechanisms underlying preneoplastic changes and cancer progression, thereby identifying novel targets for prevention, early detection, and therapeutic intervention.