The microenvironment dictates glycocalyx construction and immune surveillance

Tharp, K.; Park, S.; Timblin, G. A.; Richards, A.; Berg, J.; Twells, N.; Riley, N. M.; Peltan, E.; Shon, D. J.; Stevenson, E.; Tsui, C. K.; Palomba, F.; Lefebvre, A. E.; Soens, R.; Ayad, N.; ten Hoeve-Scott, J.; Healy, K.; Digman, M.; Dillin, A.; Bertozzi, C.; Mahal, L. K.; Swaney, D.; Cantor, J. R.; Paszek, M.; Weaver, V.

doi:10.1101/2023.06.23.546317

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bioRxiv · 10.1101/2023.06.23.546317

The microenvironment dictates glycocalyx construction and immune surveillance

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Abstract

Efforts to identify anti-cancer therapeutics and understand tumor-immune interactions are built with in vitro models that do not match the microenvironmental characteristics of human tissues. Using in vitro models 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 PointsO_LICulture medium dictates cellular mechanoresponse signatures in vitro C_LIO_LIEpithelial glycocalyx construction is mediated by Heat Shock Factor 1 (HSF1) C_LIO_LISialic acid topology dictates Natural Killer cell cytotoxicity C_LIO_LIPhysiological microenvironments reveal distinct glycobiology C_LI

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Tharp, K., Park, S., Timblin, G. A., Richards, A., Berg, J., Twells, N., Riley, N. M., Peltan, E., Shon, D. J., Stevenson, E., Tsui, C. K., Palomba, F., Lefebvre, A. E., Soens, R., Ayad, N., ten Hoeve-Scott, J., Healy, K., Digman, M., Dillin, A., Bertozzi, C., Mahal, L. K., Swaney, D., Cantor, J. R., Paszek, M., Weaver, V.. 2023-06-25. The microenvironment dictates glycocalyx construction and immune surveillance. https://doi.org/10.1101/2023.06.23.546317

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