Endoscopic Immuno-Oncology: A New Frontier in Treatment of Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most challenging malignancies to treat, largely due to late diagnosis, limited surgical options, and profound resistance to systemic therapies, all of which contribute to a five-year survival rate of approximately 9%. The dense, hypoxic, and immunosuppressive tumor microenvironment (TME) of PDAC plays a critical role in immune evasion and therapeutic failure. As conventional immunotherapies have shown limited efficacy in PDAC, attention has shifted toward local interventions capable of remodeling the TME to enhance immune responsiveness. Endoscopic ultrasound (EUS)-guided ablative therapies have emerged as promising strategies to overcome these barriers. A range of modalities-including irreversible electroporation, microwave ablation, photodynamic therapy, and cryoablation-are under investigation. Among these, radiofrequency ablation (RFA) stands out as the most promising therapy as it not only induces direct tumor cytoreduction but also promotes antigen release, triggers immunogenic cell death, and may work synergistically with systemic therapies such as immune checkpoint inhibitors and adenosine pathway blockade. This review aims to explore the evolving role of endoscopic ablative therapies with a focus on RFA as a potential platform for immune activation in pancreatic cancer.