The Role of the Microbiome in Pancreatic Cancer

Simple Summary Pancreatic cancer is deadly cancer characterized by dense stroma creating an immunosuppressive tumor microenvironment. Accumulating evidences indicate that the microbiome plays an important role in pancreatic cancer development and progression via the local and systemic inflammation and immune responses. The alteration of the microbiome modulates the tumor microenvironment and immune system in pancreatic cancer, which affects the efficacy of chemotherapies including immune-targeted therapies. Understanding the role of microbiome and underlying mechanisms may lead to novel biomarkers and therapeutic strategies for pancreatic cancer. This review summarizes the current evidence on the role of the microbiome in pancreatic cancer. Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies, with little improvement in outcomes in recent decades, although the molecular and phenotypic characterization of PDAC has contributed to advances in tailored therapies. PDAC is characterized by dense stroma surrounding tumor cells, which limits the efficacy of treatment due to the creation of a physical barrier and immunosuppressive environment. Emerging evidence regarding the microbiome in PDAC implies its potential role in the initiation and progression of PDAC. However, the underlying mechanisms of how the microbiome affects the local tumor microenvironment (TME) as well as the systemic immune system have not been elucidated in PDAC. In addition, therapeutic strategies based on the microbiome have not been established. In this review, we summarize the current evidence regarding the role of the microbiome in the development of PDAC and discuss a possible role for the microbiome in the early detection of PDAC in relation to premalignant pancreatic diseases, such as chronic pancreatitis and intraductal papillary mucinous neoplasm (IPMN). In addition, we discuss the potential role of the microbiome in the treatment of PDAC, especially in immunotherapy, although the biomarkers used to predict the efficacy of immunotherapy in PDAC are still unknown. A comprehensive understanding of tumor-associated immune responses, including those involving the microbiome, holds promise for new treatments in PDAC.