MIAMI, July7 : A new “tumor-on-a-chip” model is giving scientists a live look at how pancreatic cancer can recruit the body’s own immune cells to help tumors survive. Researchers say the findings, published in Biofabrication, an Institute of Physics journal, reveal possible new targets to weaken the cancer’s defenses and make treatments work better.
Pancreatic cancer has long been one of the most lethal cancers, in part because it hides behind a dense, protective environment that resists treatment. Now, scientists have developed a new way to see inside that environment as it functions in real time, uncovering how cancer recruits the immune system to help it survive.
The interdisciplinary research builds on the Engineering Cancer Cures™ collaboration between Sylvester Comprehensive Cancer Center, part of the University of Miami Miller School of Medicine, and the University of Miami College of Engineering. The effort focuses on developing and deploying innovative technologies for early detection, diagnosis and treatment of cancer.
Using a micro-engineered ‘tumor-on-a-chip’ model, researchers recreated the complex ecosystem surrounding pancreatic tumors and observed how cells interact dynamically. The findings reveal a critical mechanism that may explain why many therapies fail and point to new therapeutic strategies.
“For the first time, we can watch pancreatic cancer rebuild its environment in real time,” said Ashutosh Agarwal, Ph.D., senior author of the study, co-director of Engineering Cancer Cures™ for Sylvester, professor of biomedical engineering at the University of Miami and director of engineering and applied physics for the Desai Sethi Urology Institute. “It is like moving from a still image to a live broadcast. We are seeing interactions that were previously invisible, and the interactions driving treatment resistance.”
Unlike many other cancers, pancreatic tumors are not just made of cancer cells. They are surrounded by a thick network of structural and immune cells that act like both a shield and a support system. This “tumor microenvironment” blocks therapies, suppresses immune responses and helps cancer grow. Among the most important players are cancer-associated fibroblasts, cells that shape the tissue structure and release signaling molecules.
Within this ecosystem, inflammatory fibroblasts serve as amplifiers, sending signals that attract immune cells that paradoxically support tumor growth rather than fight it.
“Pancreatic cancer is an ecosystem,” said study co-leader Jashodeep Datta, M.D., pancreatic and hepatobiliary surgical oncologist, co-leader of the Gastrointestinal Site Disease Group and assistant director of transdisciplinary research at Sylvester. “If you want to treat the disease effectively, you have to understand how all of these components interact and reinforce each other.”
Traditional lab models have struggled to replicate this complexity. Flat, two-dimensional cell cultures lack structure, while animal models make it difficult to isolate specific cell interactions.
The new microfluidic platform bridges that gap. Roughly the size of a handheld device, the system recreates three-dimensional tumor architecture while allowing immune cells to flow through it, mimicking real biological conditions. The result is a dynamic, living model.
“This technology allows us to observe not just what cells are present, but how they behave and communicate over time,” said Datta. “Those dynamics are essential to understanding why pancreatic cancer is so resistant to therapy.”
The study revealed a surprising and troubling role for a specific type of immune cell known as myeloid-derived suppressor cells. Rather than attacking the tumor, these cells actively reshape the tumor environment to make it more supportive of cancer growth.
In the model, these immune cells pushed fibroblasts into an inflammatory state. Once activated, these fibroblasts released signals that further suppressed immune response and promoted tumor progression, creating a reinforcing cycle.
“We are seeing the immune system being co-opted in real time,” said Datta. “Instead of eliminating the tumor, certain immune cells are essentially helping it build stronger defenses.”
Beyond confirming known mechanisms, the research uncovered a previously underrecognized population of fibroblast cells that appear primed to become inflammatory.
These precursor cells behave like a reserve force, ready to activate under the influence of immune signals. Once triggered, they rapidly transition into cells that support tumor growth.
“These cells are already on the path toward becoming pro-inflammatory, and the immune system accelerates that transformation,” said Agarwal. “That gives us a very specific point of intervention we did not have before.”
This discovery suggests that the tumor microenvironment is not fixed, but constantly evolving, adapting quickly to signals and reshaping itself to protect the cancer.
What This Means for Future Pancreatic Cancer Treatment
Today’s therapies often focus directly on killing cancer cells. But this research suggests that targeting the interactions between immune cells and the tumor environment may be just as important.
By interrupting the signals that drive inflammation and immune suppression, researchers may be able to weaken the tumor’s protective barrier and improve the effectiveness of existing treatments.
“If we can break the communication between immune cells and the tumor environment, we may be able to make resistant cancers vulnerable again,” said Datta. “That is where we see real potential for impact.”
While the study focuses on pancreatic cancer, the technology has broader potential. Because the platform can replicate complex, dynamic environments, it could be used to study other cancers, as well as chronic inflammatory diseases.
“This is a new way of studying disease,” said Agarwal. “It gives us a powerful tool to understand and ultimately disrupt the biological systems that drive cancer.”
Read more about Sylvester’s efforts to advance cancer research through big data on the InventUM blog and follow @SylvesterCancer on X for the latest news on its research and care.
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