FIGURE 1.

Schematic illustration of different terms used to describe the tumor stroma. The tumor microenvironment (TME) of pancreatic adenocarcinoma (PDAC) includes the tumor cells in addition to the stroma. The stroma is a complex milieu of non-tumor cells, cytokines, growth factors and the proteins of extracellular matrix (ECM). The ECM consists of the non-cellular structural arrangement of the tissue and is highly proteinaceous. Cellular components of PDAC stroma include immune cells such as T-cells and macrophages, as well as stromal cells such as adipocytes and pancreatic stellate cells (PSCs) which are a source of cancer associated fibroblasts (CAFs). CAFs and, to a lesser extent, tumor cells alter the ECM composition by means of increased collagen, both fibrillar and non-fibrillar, deposition as well as laminins, hyaluronan and other proteoglycans. The pathophysiological increase of ECM protein content in the TME results in a desmoplastic reaction, generating denser, stiffer tissue than in the healthy pancreatic setting. Consequences of the desmoplastic reaction are a constrained blood vessels, infiltration around the tissue, and a corresponding reduction of fluid perfusion into the tissue, which in turn cultivates a hypoxic TME.