Tharp Kevin M, Park Sangwoo, Timblin Greg A, Richards Alicia L, Berg Jordan A, Twells Nicholas M, Riley Nicholas M, Peltan Egan L, Shon D Judy, Stevenson Erica, Tsui Kimberly, Palomba Francesco, Lefebvre Austin E Y T, Soens Ross W, Ayad Nadia M E, Hoeve-Scott Johanna Ten, Healy Kevin, Digman Michelle, Dillin Andrew, Bertozzi Carolyn R, Swaney Danielle L, Mahal Lara K, Cantor Jason R, Paszek Matthew J, Weaver Valerie M
Center for Bioengineering and Tissue Regeneration, Department of Surgery, University of California San Francisco, San Francisco, CA 94143, USA.
Field of Biophysics, Cornell University, Ithaca, NY 14850, USA.
Res Sq. 2023 Aug 16:rs.3.rs-3164966. doi: 10.21203/rs.3.rs-3164966/v1.
Efforts to identify anti-cancer therapeutics and understand tumor-immune interactions are built with models that do not match the microenvironmental characteristics of human tissues. Using 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.
识别抗癌疗法和理解肿瘤-免疫相互作用所做的努力是基于与人体组织微环境特征不匹配的模型构建的。使用模拟健康或癌组织物理特性的模型以及生理相关的培养基,我们证明微环境的化学和物理特性调节糖萼的组成和拓扑结构。值得注意的是,我们发现微环境物理特性的癌症相关和年龄相关变化足以通过糖萼的拓扑结构调节免疫监视,这是一种以前未知的现象,只有在生理相关的培养基中才能观察到。