Researchers at Georgetown's Lombardi Comprehensive Cancer Center have identified a way in which pancreatic cancer cells alter the behavior of nearby immune cells, potentially opening new avenues for treatment. The findings were published on January 16, 2026, in the journal Signal Transduction and Targeted Therapy.
Pancreatic cancer remains one of the most lethal cancers in the United States. In 2025, there were about 67,440 new cases and approximately 51,980 deaths from the disease. It is now the third leading cause of cancer-related deaths in the country and has a five-year survival rate of just 13 percent. Incidence rates are rising, particularly among women, with factors such as diet, lifestyle, and obesity being linked to increased risk.
The study led by Cheema's team investigated why pancreatic tumors often resist current therapies. Pancreatic tumors are known for creating an environment that weakens the body's immune response and resists both chemotherapy and immunotherapy due to dense tissue around the tumor and an immunosuppressive microenvironment.
The researchers focused on extracellular vesicles—tiny particles released by cells—to understand how cancer evades immune defenses. They found that while healthy pancreatic cells also release these vesicles, only cancer cells send out specific microRNA molecules within them that can suppress immune responses.
Specifically, they discovered that pancreatic cancer cells package a micro-RNA molecule called miR-182-5p into their vesicles. When these vesicles reach macrophages—immune cells that usually help destroy harmful cells—the macrophages absorb them and undergo changes: their normal tumor-fighting activity is switched off while pathways that suppress immune responses are activated. As a result, these macrophages begin to support tumor growth instead of combating it.
The team also demonstrated that blocking miR-182-5p could reverse this effect. In mouse models of pancreatic cancer, injecting nanoparticles designed to block miR-182-5p restored the ability of macrophages to attack tumor cells.
"Our findings show that pancreatic cancer actively rewires macrophages using microRNA as signaling molecules. By targeting those signals, we can restore the immune system's ability to fight the tumor," Cheema said. "Additionally, this approach did not broadly damage healthy cells, suggesting it could be a safer and more targeted strategy than blocking all vesicles released from cancer cells as has been suggested by other studies."
The communication pathway between cancer cells and immune cells described in this research may not be unique to pancreatic cancer; similar mechanisms might exist in other types of tumors as well. This suggests potential broader applications for the therapeutic strategy proposed by Cheema’s team.
A significant challenge ahead will be improving drug delivery specifically to pancreatic tumors without harming normal tissue. Cheema stated that future work will focus on developing nanoparticle-based delivery systems tailored to target human pancreatic cancer cells.
"While more research is needed before this approach reaches patients, the findings offer new hope for improving outcomes in pancreatic cancer," Cheema added.
Other contributors from Georgetown include Baldev Singh (also named as co-inventor on a provisional patent application filed by Georgetown University), Pankaj Gaur, Pritha Bose, Yanjun Zhang, Yaoxiang Li, Zihao Zhang, Jeyalakshmi Kandhavelu, William Klotzbier, Meth Jayatilake, Shivani Bansal, Mohd Farhan, Sunain Deol, Partha P Banerjee, Keith Unger and Seema Gupta; Vivek Verma is at the University of Minnesota in Minneapolis.
Cheema and her co-authors reported no personal financial interests related to this study. The research received partial support from NIH grant P30-CA051008.
