Angiogenic Properties of NK Cells in Cancer and Other Angiogenesis-Dependent Diseases

Abstract

The pathogenesis of many serious diseases, including cancer, is closely related to disturbances in the angiogenesis process. Angiogenesis is essential for the progression of tumor growth and metastasis. The tumor microenvironment (TME) has immunosuppressive properties, which contribute to tumor expansion and angiogenesis. Similarly, the uterine microenvironment (UME) exerts a tolerogenic (immunosuppressive) and proangiogenic effect on its cells, promoting implantation and development of the embryo and placenta. In the TME and UME natural killer (NK) cells, which otherwise are capable of killing target cells autonomously, enter a state of reduced cytotoxicity or anergy. Both TME and UME are rich with factors (e.g., TGF-β, glycodelin, hypoxia), which support a conversion of NK cells to the low/non-cytotoxic, proangiogenic CD56brightCD16low phenotype. It is plausible that the phenomenon of acquiring proangiogenic and low cytotoxic features by NK cells is not only limited to cancer but is a common feature of different angiogenesis-dependent diseases (ADDs). In this review, we will discuss the role of NK cells in angiogenesis disturbances associated with cancer and other selected ADDs. Expanding the knowledge of the mechanisms responsible for angiogenesis and its disorders contributes to a better understanding of ADDs and may have therapeutic implications.