Pancreatic Cancer Sends Secret Signals That Sabotage Immune Cells

Researchers have uncovered a stealthy way pancreatic cancer disarms the immune system, using tiny molecular messengers to turn defenders into allies.

Researchers at Georgetown’s Lombardi Comprehensive Cancer Center have identified a surprising way pancreatic cancer cells influence the immune system. Their work shows that cancer cells release microscopic particles containing specific microRNA molecules that alter the behavior of nearby immune cells known as macrophages.

Instead of attacking the tumor, these reprogrammed cells begin to support its growth. Experiments in cells and mice helped the research team identify this process and suggest that it may be possible to interrupt it, offering a potential path toward improved pancreatic cancer treatment.

“Our approach focuses on blocking adverse outcomes of microRNA-based communication between pancreatic cancer cells and immune cells,” says Amrita Cheema, PhD, professor, Departments of Oncology, Biochemistry, Molecular and Cellular Biology and Radiation Medicine at Georgetown and senior author of the study. “By disrupting these channels of communication, we could reprogram the immune cells and restore their ability to fight cancer, resulting in meaningful reductions in pancreatic tumor growth.”

The study was recently published in the Nature journal Signal Transduction and Targeted Therapy.

The Growing Burden of Pancreatic Cancer

Pancreatic cancer remains one of the deadliest cancers in the United States. In 2025, an estimated 67,440 people were newly diagnosed, and approximately 51,980 deaths were recorded. These figures make it the third leading cause of cancer-related deaths nationwide, with a five-year survival rate of just 13 percent. Rates of aggressive disease continue to rise, particularly among women, and have been associated with factors such as diet, lifestyle, and obesity.

One reason pancreatic cancer is so difficult to treat is its ability to suppress the body’s natural immune defenses. The tumor is surrounded by dense tissue and exists within a highly immunosuppressive environment. Together, these features limit the effectiveness of chemotherapy and immunotherapy by preventing drugs and immune cells from reaching the cancer.

To better understand why pancreatic tumors resist treatment, Cheema’s team examined extracellular vesicles, which are tiny particles released by cells. Although healthy pancreatic cells also produce these vesicles, the researchers found that cancer cells uniquely use them to deliver signals that actively weaken immune responses.

Tiny Vesicles With a Powerful Effect

The investigators discovered that pancreatic cancer cells load their vesicles with a particular microRNA molecule known as miR-182-5p. Once released, these vesicles can travel to nearby macrophages, immune cells that typically play a role in identifying and destroying cancer cells.

When macrophages take in vesicles containing miR-182-5p, their function changes. Signals that normally activate immune responses are reduced, while pathways that dampen immunity are increased. Through this shift, macrophages stop acting against the tumor and instead begin to promote its growth.

Reversing Tumor-Friendly Signals

Encouragingly, the researchers also showed that blocking miR-182-5p can reverse this process. Using established mouse models of pancreatic cancer, the researchers showed that injecting them with nanoparticles designed to block miR182-5p greatly helped restore the tumor cell killing function of macrophages.

“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 says. “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 that the scientists have elucidated in this study is not unique to pancreatic cancer. Because many tumors use similar messaging systems to evade immune attacks, the researchers’ proposed therapeutic strategy could potentially be adapted to treat other types of cancer as well.

One major challenge ahead is to improve the delivery of drugs to pancreatic tumors without deleteriously affecting normal cells. Therefore, the next steps, according to Cheema, will include developing nanoparticle-based novel delivery systems to selectively 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,” says Cheema.

Reference: “Extracellular vesicle-derived miRNA-182-5p educates macrophages towards an immunosuppressive phenotype in pancreatic cancer” by Baldev Singh, 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, Seema Gupta, Vivek Verma and Amrita K. Cheema, 16 January 2026, Signal Transduction and Targeted Therapy.
DOI: 10.1038/s41392-025-02559-3

A provisional patent application has been filed by the Office of Technology Commercialization at Georgetown University. Along with Cheema, Baldev Singh has been named as a co-inventor. Cheema and her co-authors report having no other personal financial interests related to the study.

This work was partially supported by NIH grant P30-CA051008.

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