The role of inflammatory cells in fostering pancreatic cancer cell growth and invasion

Abstract

The pancreatic ductal adenocarcinoma (PDAC) microenvironment accommodates a variety of cell types and a plethora of complex interactions between tumor cells, host cells and extracellular matrix (ECM) components. Here we review the role of inflammatory cells, in particular mast cells, myeloid-derived suppressor cells, macrophages, T regulatory cells, T helper cells and neutrophils. The picture that emerges is that of a tumor microenvironment, in which the immune response is actively suppressed, and inflammatory cells contribute in a variety of ways to tumor progression.

Keywords: T helper cells; inflammation; macrophages; mast cells; myeloid-derived suppressor cells; neutrophils; regulatory T cells; stroma.

Figure 1

Inflammatory cell infiltration promotes growth and invasion in pancreatic cancer. Desmoplastic stroma accumulates as tumorigenesis progresses, increasing vascular formation and the production of collagen while recruiting cells of the immune system to enhance tumor growth. Mast cells and activated tumor associated macrophages (TAMs) localize at the leading edge of the tumor where they can accelerate tumor invasion, and TAMs are thought to enhance lymphatic metastasis and angiogenesis. Myeloid derived suppressor cells (MDSCs), likewise, accumulate at the invasive front and inhibit CD8⁺ cytotoxic T cells, enabling immune evasion. Regulatory T cells (Tregs), which also suppress immune function, can be found in relatively high abundance in pancreatic ductal adenocarcinoma (PDAC). The presence of Th2 T helper cells in greater numbers than Th1 has also been linked to increased tumor growth. PanIN = Pancreatic intraepithelial neoplasia.