45 Radiotherapy could do more than destroy tumour cells when used alongside immunotherapy, according to a review exploring new strategies for treating localised pancreatic cancer. The study published in Nature Reviews Gastroenterology & Hepatology on 2nd September 2026, the review was conducted by researchers from GIGA and Liège University Hospital, together with colleagues from Gustave Roussy in Paris, France, and Fox Chase Cancer Center in Philadelphia, USA. Coordinated by Dr Gilles Colin and Dr Pierre Foidart, the paper, titled Challenges and opportunities in combining radiotherapy and immunotherapy for localised pancreatic cancer, examines findings from basic and clinical research. The researchers focus on how radiotherapy can modify antitumour immune responses and how those effects could be harnessed alongside immunotherapy to reduce the risk of metastatic relapse. Pancreatic cancer is resistant to many treatments and has a particularly poor prognosis, even when diagnosed at a localised stage. Surgery may be possible when the tumour has not spread, but the risk of recurrence remains high. A major challenge is the tumour microenvironment, which contains a dense stromal compartment and biological mechanisms that suppress immune cell activity. As a result, immunotherapies that have transformed treatment for several other cancers have so far shown limited effectiveness in pancreatic cancer. Conventional radiotherapy has also provided only modest benefits, highlighting the need for new approaches to its use. The review highlights biological effects of radiotherapy that could be used more effectively. Under specific conditions, radiation can make cancer cells more visible to the immune system, promote the activation of immune effector cells, and alter the tumour microenvironment to support antitumour immunity. This means the effectiveness of combined treatment may depend not simply on administering radiotherapy and immunotherapy together, but on how radiotherapy is delivered. Radiation dose, fractionation, treatment sequencing, irradiation precision, and target volume selection could all influence the resulting immune response. “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 optimise the interaction between these two treatment modalities,” explains Dr Foidart. The review outlines several approaches being assessed in preclinical and clinical studies, including more targeted and better tolerated forms of radiotherapy, next-generation immunotherapies, therapeutic vaccines, and treatments designed to reprogramme the tumour microenvironment. Researchers are also investigating inhibitors targeting biological pathways involved in pancreatic cancer, particularly those associated with KRAS, a frequently altered protein in the disease. The researchers say these approaches could help overcome biological mechanisms that contribute to treatment resistance in pancreatic cancer. Future progress will also depend on identifying which patients are most likely to benefit from these combinations. Predictive biomarkers, circulating tumour DNA analysis, and adaptive clinical trial designs could help personalise treatment and determine which therapeutic strategies are most effective for individual patients. “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 Colin. The review provides a framework for further research combining radiotherapy, immunotherapy, precision medicine, and technological innovation. The researchers argue that these fields need to advance together to address the resistance mechanisms that characterise pancreatic cancer. In the long term, such strategies could improve local disease control, limit the emergence of clinically undetectable metastatic lesions already present at diagnosis, and extend survival. The researchers from the University of Liège and their international partners emphasise that optimising radiotherapy delivery will be essential to achieving better outcomes from its combination with immunotherapy in localised pancreatic cancer.