Breast Cancer-on-a-Chip Models Cancer-Immune Interactions

A team from the Terasaki Institute for Biomedical Innovation has designed and tested a system to model cancer-immune interactions. The system features spherical aggregates of breast cancer cells in a custom-fabricated, 3D printed, transparent chip with conical microwells.

"The features of our microwell-based chip is the key to our successful development of an immunoactive tissue model," said Wujin Sun, Ph.D., senior author of a paper published in Nan-Micro Small last week. "The chip's transparency allows for direct microscopic observation. And its design allows for high-volume testing, which lends itself well to the rapid screening of immunotherapeutic drugs."

The automated system, which consists of an array of miniaturized bioreactors, measures cytokine levels. When the system was tested with anti-checkpoint protein drugs, the results showed that upon incubation of the breast cancer cells with the T-cells, cytokine production was increased by the use of the drugs, demonstrating their effectiveness in activating the T-cells.

The team also used their breast cancer chip was to assess the breast cancer cells' effect on stimulated T-cells. The T-cells were fluorescently labeled and added to the breast cancer cells in the microwells. These breast cancer cells normally cause rupture of the T-cells, but experiments conducted with checkpoint inhibitor drugs showed that the drugs increased T-cell viability in the cultures, visually demonstrating how they can counter the effects of T-cell rupture by tumor cell interaction.

The system was also used to observe how T-cells infiltrated the breast cancer cellular spheres; this type of infiltration is a measure of a T-cell's anti-tumor activity and viability. After labeling each group of cells with separate dyes and mixing them in the chip's microwells, T-cell infiltration could be directly visualized using high-resolution fluorescence microscopy. Experiments conducted with checkpoint inhibitor drugs indicated that there were increased numbers of T-cells and deeper penetration into the breast cancer cells in the presence of the drugs.