| Pancreatic cancer is a highly aggressive malignancy with an extremely poor prognosis. While conventional treatments provide limited benefit, research into immunotherapy is actively underway. However, its distinct immunosuppressive tumor microenvironment poses a major challenge and leads to prevalent immunotherapy resistance. This resistance stems from characteristics such as low immunogenicity—manifested by a low tumor mutational burden, impaired antigen presentation, and upregulated immune-inhibitory molecules—and is further compounded by a microenvironment composed of stromal elements, immunosuppressive cell populations, and soluble factors that collectively foster tumor progression. The clinical utility of immune checkpoint inhibitors as monotherapy remains constrained. To address this challenge, synergistic combination immunotherapy strategies have been extensively evaluated in clinical trials and have demonstrated survival benefits, representing a pivotal direction in the field. Meanwhile, novel therapeutic approaches designed to overcome immune tolerance are under continuous exploration. This review summarizes the current clinical progress of multimodal combination strategies—including immunotherapy combined with chemotherapy or targeted therapy—and discusses emerging immunotherapies such as novel effector molecules, cellular therapies, and tumor microenvironment remodeling. Finally, future perspectives for immunotherapy in pancreatic cancer are presented. |
