Seminar

Glycosylation dependent cellular communication in the tumor microenvironments

Yvette van Kooyk

Alterations in glycosylation is a hallmark in cancer to regulate cellular communication (migration metastasis) but also immune differentiation, activation and silencing. We studied the glycosylation machinery in clinical data sets of cancer, in particular pancreatic cancer and melanoma, through transcriptomic analysis of around 350 glycosylation genes that code for glycan donors, enzymes, transporters, carriers. We investigated their presence in tumor biopsies, and analysed their impact on myeloid and lymphoid immune cells differentiation and function. In particular specific sialyltransferases and enzymes of the donor pathway involved in sialylation, had impact on survival and tumor growth when their expression was reduced, and were associated with altered T cell infiltration and inflammatory macrophage subsets in the TME. Interaction with tumor and stromal expressed sialoglycans lead to binding of Siglec-7, -9, -10 and -15. We conclude that interfering with sialic acid/Siglec axis has great impact on reducing survival benefit, and in melanoma may predict response to immune checkpoint blockade.