The microenvironment dictates glycocalyx construction and immune surveillance
Abstract
Summary: Efforts to identify anti-cancer therapeutics and understand tumor-immune interactions are built within vitromodels that do not match the microenvironmental characteristics of human tissues. Usingin vitromodels which mimic the physical properties of healthy or cancerous tissues and a physiologically relevant culture medium, we demonstrate that the chemical and physical properties of the microenvironment regulate the composition and topology of the glycocalyx. Remarkably, we find that cancer and age-related changes in the physical properties of the microenvironment are sufficient to adjust immune surveillance via the topology of the glycocalyx, a previously unknown phenomenon observable only with a physiologically relevant culture medium. Key Points: Culture medium dictates cellular mechanoresponse signatures in vitro Epithelial glycocalyx construction is mediated by Heat Shock Factor 1 (HSF1) Sialic acid topology dictates Natural Killer cell cytotoxicity Physiological microenvironments reveal distinct glycobiology
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