New ‘Tumor-on-a-Chip’ Technology Reveals How Solid Cancers Evade Immune Attacks
Researchers at the University of Pennsylvania have developed a groundbreaking “tumor-on-a-chip” platform that provides an unprecedented look at the mechanisms cancers use to resist attacks from the immune system. This innovation could significantly accelerate the creation of more effective immunotherapies, particularly for solid tumors, which account for more than 90% of all cancer cases.
Overcoming the Barrier of Solid Tumors
Although CAR T-cell therapy has fundamentally changed the treatment landscape for blood cancers, such as lymphoma and leukemia, it has seen limited success when applied to solid tumors. According to Professor Dan Dongeun Huh of Penn’s School of Engineering and Applied Science, this disparity is caused by the tumor microenvironment (TME)—a sophisticated and protective ecosystem that shields cancer cells and hinders the efficacy of immune therapies.
To better understand and penetrate these defenses, Huh’s team engineered a transparent, microengineered device designed to replicate a living, vascularized human lung tumor. This “tumor-on-a-chip” enables scientists to observe in real time how engineered immune cells, including CAR T-cells, interact with cancer cells and navigate the obstacles within the TME.
“It’s like having a window into the battlefield of cancer immunotherapy,” Professor Huh explained. “People can literally watch CAR T-cells infiltrate the tumor, strike their targets, and sometimes fail.”
Identifying the ‘Aid’ Signals
Through this platform, the research team discovered that endothelial cells—the cells that line the blood vessels of a tumor—emit short-lived chemical “help” signals designed to attract CAR T-cells to the site. However, when these signals degrade and fade, the immune cells lose their way, failing to reach their targets.
Using multiomics analysis—which integrates metabolic, proteomic, and genomic data—alongside advanced bioinformatics, the team identified the enzyme DPP4 as a critical factor in this failure, as it is responsible for degrading these essential signaling molecules.
A Potential Solution in a Diabetes Drug
The study found a potential way to maintain these signals using vildagliptin, a medication already approved for the treatment of type 2 diabetes. By introducing the drug, the researchers were able to prevent the breakdown of the signaling molecules, which allowed a greater number of CAR T-cells to successfully locate and attack the tumor.
This discovery underscores the potential for repurposing existing medications to enhance the precision of cancer treatments. By improving the ability of immune cells to navigate the complex environment of solid tumors, these findings could expand the reach of immunotherapy to a much larger population of cancer patients.
