Abstract:Pancreatic cancer (PC) is highly malignant, with an insidious onset and poor prognosis. Current treatment measures often fail because of the immunosuppressive characteristics of the tumor microenvironment (TME), leading to recurrence and resistance. The characteristics of the TME frequently affect the efficacy of tumor immunotherapy, especially in suppressive immune microenvironments, where immune evasion and immune tolerance of the tumor commonly occur. The progression of PC result from the combined effects of the microbiota, the host’ s genetic background, and environmental factors. The microbiota plays a central regulatory role by reshaping the immune microenvironment, and targeting specific microbiota to modulate immune cell function can enhance the efficacy of immune checkpoint inhibitors. This review focuses on the immune microenvironment in PC, analyzing the differences in microbiota associated with gastrointestinal tumors, and summarizes research progress on the mechanisms by which the microbiota influences the PC immune microenvironment and enhances the effectiveness of immunotherapy. The review also examines the potential of the microbiota and its metabolic pathways for improving the suppressive immune microenvironment in PC, and discusses the regulatory mechanisms of the microbiota in PC immune responses, aiming to provide new personalized immunotherapeutic strategies for patients with PC.