Pancreatic cancer is one of the hardest cancers to treat. Even when it’s caught early and the tumour can be removed by surgery, it often comes back. Now, researchers are suggesting that radiotherapy, long thought of simply as a way to kill cancer cells, might have a much bigger role to play by waking up the immune system to join the fight.
A new review published in Nature Reviews Gastroenterology & Hepatology lays out this idea in detail. Led by researchers from GIGA and Liège University Hospital, the paper argues that radiotherapy should be reimagined as a tool that can boost immunotherapy, especially in pancreatic cancer where current treatments often fall short.
Why Pancreatic Cancer Is So Hard to Treat
Pancreatic cancer has stubbornly resisted many of the breakthroughs that have transformed care for other cancers. Even when surgery is possible, the chance of relapse is high. A big part of the problem lies in what’s called the tumour microenvironment: the dense tissue surrounding the cancer that acts almost like a shield, blocking immune cells from doing their job.
That same shield helps explain why immunotherapy, which has been a game-changer for cancers like melanoma or certain lung cancers, has had only limited success in pancreatic cancer so far. Radiotherapy, delivered in the usual way, also hasn’t produced the dramatic gains seen elsewhere.
Turning Radiotherapy Into an Immune System Ally
The authors argue that radiotherapy has effects far beyond simply damaging tumour cells, and these effects are not being used to their full potential. When delivered in just the right way, radiation can:
- Make cancer cells more “visible” to the immune system
- Activate immune cells that attack tumours
- Reshape the environment around the tumour so immune cells can get in and work
The trick isn’t just to add radiotherapy and immunotherapy together like two ingredients in a recipe, but to redesign how radiotherapy is delivered to maximise its ability to kickstart an immune response. That means paying careful attention to the dose used, how it’s split up (fractionation), the timing with other treatments, how precisely it’s aimed, and which parts of the body are targeted.
“It is not enough to simply combine radiotherapy and immunotherapy. It is equally important to better understand how radiotherapy delivery parameters influence the immune response in order to optimize the interaction between these two treatment modalities,” explains Dr Pierre Foidart, who co-coordinated the review with Dr Gilles Colin.
New Approaches on the Horizon
The review highlights several promising strategies already being tested in laboratories and clinical trials. Some involve more precise, better-tolerated forms of radiotherapy. Others combine radiation with next-generation immunotherapies, therapeutic cancer vaccines, or drugs designed to break down the protective “shield” around pancreatic tumours.
Researchers are also exploring treatments that target key biological pathways involved in pancreatic cancer, especially those linked to KRAS, a protein that is faulty in a large proportion of pancreatic cancer cases.
Personalising Treatment for Each Patient
A key message from the review is that pancreatic cancer treatment will need to become much more personalised. Not every patient will respond the same way, and figuring out who is most likely to benefit from a given combination is crucial.
Tools like predictive biomarkers (clues in a patient’s biology that signal who will respond), tests that analyse tumour DNA circulating in the blood, and new flexible clinical trial designs could all help match patients with the right combinations.
“Pancreatic cancer remains a major challenge in oncology. However, recent advances now allow us to view radiotherapy from an entirely new perspective. By considering it as a platform capable of modulating both the tumour microenvironment and responsiveness to immunotherapy, we are opening new avenues to improve disease control,” says Dr Gilles Colin.
A Roadmap, Not Just a Review
More than a summary of what’s known, the paper is intended as a guide for future research. The authors argue for an integrated approach that brings together radiotherapy, immunotherapy, precision medicine, and new technologies to overcome the many ways pancreatic cancer resists treatment.
If successful, these combined strategies could help control the disease locally, prevent hidden metastases from taking hold after surgery, and ultimately give patients with one of the most feared cancers a better chance of longer survival.
Colin, G., Streel, S., Deutsch, E., Galluzzi, L., & Foidart, P. Radiotherapy as an immunological platform in pancreatic cancer: optimising combinations with immunotherapy. Nature Reviews Gastroenterology & Hepatology (2026). DOI: 10.1038/s41575-026-01250-4