Involvement of the Gut Microbiome in the Local and Systemic Immune Response to Pancreatic Ductal Adenocarcinoma

Simple Summary One of the reasons that pancreatic cancer is such a deadly disease is that it is able to evade the body's usual defence system (the immune system). It has been shown that the population of microorganisms in the human gut (the gut microbiome) plays a role in regulating the human immune system. This article outlines the ways in which the gut microbiome influences the immune system in pancreatic cancer both within the bloodstream (systemic) and around the pancreatic tumour itself (local). These are important mechanisms because greater understanding of these will direct the development of future treatments for pancreatic cancer. It is possible that some of these treatment options will target the gut microbiome in order to boost the immune system's response to pancreatic cancer.Abstract The systemic and local immunosuppression exhibited by pancreatic ductal adenocarcinoma (PDAC) contributes significantly to its aggressive nature. There is a need for a greater understanding of the mechanisms behind this profound immune evasion, which makes it one of the most challenging malignancies to treat and thus one of the leading causes of cancer death worldwide. The gut microbiome is now thought to be the largest immune organ in the body and has been shown to play an important role in multiple immune-mediated diseases. By summarizing the current literature, this review examines the mechanisms by which the gut microbiome may modulate the immune response to PDAC. Evidence suggests that the gut microbiome can alter immune cell populations both in the peripheral blood and within the tumour itself in PDAC patients. In addition, evidence suggests that the gut microbiome influences the composition of the PDAC tumour microbiome, which exerts a local effect on PDAC tumour immune infiltration. Put together, this promotes the gut microbiome as a promising route for future therapies to improve immune responses in PDAC patients.