Abstract
Cancer is one of the leading causes of death worldwide. The immune system plays an important role in all steps of cancer development, growth and spreading as was repeatedly proven in a variety of experimental and clinical studies. Among the immune cells, Natural Killer cells, or NK cells, are critical to the innate immunity as one of the key effector cells of cancer immunosurveillance. NK cells’ role in the immunity against cancer is mediated by exerting cytotoxicity and secreting a variety of cytokines to inhibit tumor growth and progression. Therefore, one of essential pathways of cancerogenesis and tumor escape from immune recognition and elimination may be associated with NK cell defects. In fact, the abnormal NK cells and their functional impairment in patients with cancer may contribute to the progression of different cancer types. In particular, the exhaustion of NK cells that represents lower cytotoxicity and impaired cytokine production may serve as a predictor for the occurrence of several cancers. The authors have evaluated potential molecular defects in NK cells isolated from healthy donors and cancer patients by assessing expression of key molecular regulators of NK cells, including c-Myc, Notch1, Notch2, p-53, Cdk6 and Rb. The results revealed a reduced expression of c-myc proto-oncogene and Notch1 signaling in NK cells in cancer patients. It was also uncovered that molecular abnormalities were not limited to NK cells but could be also seen in other lymphocytes, particularly T cells. It is conceivable that correction of NK cell molecular defects and functional rescue of NK cells will be great promise for cancer treatment.
Keywords
NK cells, c-Myc, Notch1.2, Lung cancer, Gastric cancer, STAT3, Cdk6