Exploring the glycobiology of immune response in colitis-associated colorectal cancer

ALEJANDRO J. CAGNONI; GATTO, SABRINA; GIROTTI, ROMINA; MORALES, ROSA; MARIA MAY; MARIÑO, KARINA V.; CUTINE, ANABELA; MAZZEO, CHRISTIAN; RABINOVICH, GABRIEL A.

Brisbane

Congreso; International Congress on mucosal Immunology; 2019

Society of Mucosal Immunology

Inflammatory Bowel Diseases are chronic, relapsing and remitting intestinal inflammatory pathologies that have been associated with an increased risk of colorectal cancer, a multifactorial pathology where genetic mutations, diet, microbiota and intestinal inflammation are crucial factors that modulate disease outcome. During the last decades, aberrant glycosylation has become an important hallmark of inflammation and tumor progression. In this work, we aimed at studying the effect of the inflammatory microenvironment over the gut glycobiology during colitis-associated colorectal cancer (CACRC) progression. We evaluated the association between intestinal inflammation and neoplastic development, with special emphasis on the interaction between the intestinal glycome and Galectin-1, as this glycan-binding protein exerts important roles in CRC progression. With this purpose, we studied colitis and CACRC progression in Wild-type and Galectin-1 KO mice, by administration of azoxymethane as carcinogen and DSS for colitis induction. Wasting disease was monitored and, after sacrifice, we analyzed tumors size, immune infiltrate and cytokine profile. We found that Galectin-1-lacking mice develop an improved anti-tumor immune response, with an increase in activated CD4+ and CD8+ T cells, higher expression of IL-6, IFN-γ and lower expression of TGF-β.Furthermore, transcriptomic analyses of murine glycogenes expression of tumors evidenced significant differences in several glycosyltransferases. In addition, immunophenotype studies showed an increase in monocytes and CD4+ T cells in tumor infiltrates of Gal-1 KO mice. Moreover, we carried out a meta-analysis for mouse models of sporadic CRC and CACRC, which showed a differential glycogene expression pattern. Finally, we expanded the significance of our results by analyzing public databases for human CRC samples.