Mechanisms of Immune Cell Dysregulation in Pancreatic Ductal Adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive form of pancreatic cancer with low five-year overall survival rates of ~10% from diagnosis. The immune ‘cold’ tumor microenvironment (TME) of PDAC is a key contributor to tumor progression, featuring immunosuppression in conjunction with a reactive stroma. The immune composition of the TME is highly tumor-promoting, with the presence of immunosuppressive cells and the absence of effector and cytotoxic immune cells. Further to this, the active stroma region of the tumors contains transformed fibroblasts which communicate with tumor and immune cells to further enhance immunosuppression. Fundamental cellular processes such as T cell exhaustion, metabolic signaling, epigenetic modifications, and a series of genetic mutations can all contribute to PDAC progression and poor patient outcomes. This review describes the key mechanisms behind immune dysregulation in PDAC, highlighting the importance of this area and the essential research that is necessary.