Mast cell modulation of the tumor microenvironment

Abstract

Mast cells are myeloid derived immune effector cells that have been most widely studied in the context of allergic disease. However, over recent years it has become apparent that they also play critical roles in the regulation of tissue remodelling and host defence. In solid tumors, mast cells are abundant at the tumor periphery in close proximity to blood vessels and are frequently considered to function in a tumor promoting capacity. They release potent angiogenic cytokines that augment tumor blood vessel formation, tumor enhancing growth factors and tissue-degrading enzymes that enable tumor metastasis. Mast cells can also release mediators in the tumor microenvironment that enhance aspects of immune suppression, such as interleukin 10. These observations have led to the consideration of inhibiting mast cells as an approach to cancer therapy. In marked contrast to this negative picture of mast cells in tumors, some studies of human disease have suggested that increased mast cell numbers can be associated with an improved prognosis. It has also been demonstrated, in mouse models, that mast cells might be important targets for immune activation during immunotherapy. Since mast cells are resistant to radiation and normally serve a sentinel cell role recruiting effector cells such as natural killer cells and T cells to sites of infection, they might have substantial potential as an additional target for therapy in the context of more traditional treatments. Our understanding of mast cells in human tumor settings is limited, but there remain excellent opportunities to attempt to modulate mast cell function as a new approach to therapy.