The Poorly Immunogenic Tumor Microenvironment of Pancreatic Cancer: The Impact of Radiation Therapy, and Strategies Targeting Resistance

Abstract

Pancreatic cancer is one of the most lethal cancers, due to its uniquely aggressive behavior and resistance to therapy. The tumor microenvironment of pancreatic cancer is immunosuppressive, and attempts at utilizing immunotherapies have been unsuccessful. Radiation therapy (RT) results in immune activation and antigen presentation in other cancers, but in pancreatic cancer has had limited success in stimulating immune responses. RT activates common pathways of fibrosis and chronic inflammation seen in pancreatic cancer, resulting in immune suppression. Here we describe the pancreatic tumor microenvironment with regard to fibrosis, myeloid and lymphoid cells, and the impact of RT. We also describe strategies of targeting these pathways that have promise to improve outcomes by harnessing the cytotoxic and immune-activating aspects of RT.

Membrane Lipid Derivatives: Roles of Arachidonic Acid and Its Metabolites in Pancreatic Physiology and Pathophysiology

“…The tumor microenvironment (TME) is defined as the environment and/or conditions that surround a population of cells that form a tumor [132]. This environment includes blood vessels, immune cells, fibroblasts, stellate cells, signaling molecules, respiratory gases and the extracellular matrix, all of which participate as constituents of the stroma [133]. In cancer, the stroma plays an important role in contributing to the development of malignant cells [131].…”