Microphysiologically Engineered Vessel-Tumor Model to Investigate Vascular Transport Dynamics of Immune Cells
Yuwen Zhao, Yue Wu, Khayrul Islam, Ratul Paul, Yuyuan Zhou, Xiaochen Qin, Qiying Li, Yaling Liu
Abstract
Cancer immunotherapy has emerged as a promising therapeutic strategy to combat cancer effectively. However, it is hard to observe and quantify how this in vivo process happens. Three-dimensional (3D) microfluidic vessel-tumor models offer valuable capability to study how immune cells transport during cancer progression. We presented an advanced 3D vessel-supported tumor model consisting of the endothelial lumen and vessel network for the study of T cells' transportation. The process of T cell transport through the vessel network and interaction with tumor spheroids was represented and monitored in vitro. Specifically, we demonstrate that the endothelial glycocalyx serving in the T cells' transport can influence the endothelium-immune interaction. Furthermore, after vascular transport, how programmed cell death protein 1 (PD-1) immune checkpoint inhibition influences the delivered activated-T cells on tumor killing was evaluated. Our in vitro vessel-tumor model provides a microphysiologically engineered platform to represent T cell vascular transportation during tumor immunotherapy. The reported innovative vessel-tumor platform is believed to have the potential to explore the tumor-induced immune response mechanism and preclinically evaluate immunotherapy's effectiveness.