This microphysiological system, which mimics in vivo stromal and vascular barriers, can be used to evaluate potentiation of immune chemotaxis into tumors while probing for vascular responses to potential therapeutics. As a final control, we show that blocking ICAM-1 interferes with T-cell adhesion and chemotaxis. In addition, incorporating this rest recovers endothelial activation in response to rhCXCL12. Adopting a T-cell activation protocol with a rest period enables proliferative burst prior to introducing T-cells into chips and enhances assay sensitivity. Here, activated T-cells extravasate and migrate in response to gradients of rhCXCL11 and rhCXCL12. The described assay consists of a HUVEC-derived vascular tubule cultured under rocking flow, through which T-cells are added a collagenous stromal barrier, through which T-cells migrate and a chemoattractant/tumor (HCC0827 or NCI-H520) compartment. Presented here is a 3D chemotaxis assay, in a lung tumor-on-chip model with 3D endothelium (LToC-Endo), to address this need. While transwell and spheroid platforms have been employed, these models lack flow and endothelial barriers, and cannot faithfully model T-cell adhesion, extravasation and migration through 3D tissue. The correlation between increased T-cell infiltration and positive patient outcomes has motivated the search for therapeutics promoting T-cell infiltration.

Lung cancer is a leading cause of death worldwide, with only a fraction of patients responding to immunotherapy.

Chip ingram titus