Notch signaling defects in NK cells in patients with cancer.

Altered expressions of proto-oncogenes have been reported during normal lymphocytes mitogenesis and in T and B lymphocytes in patients with autoimmune diseases. We have recently demonstrated a significantly decreased expression of c-kit and c-Myc in NK cells isolated from patients with cancer, which might be related to the functional deficiency of NK cells in the tumor environment. Here, focusing on the regulatory mechanisms of this new clinical phenomenon, we determined expression of c-Myc, Notch1, Notch2, p-53, Cdk6, Rb and phosphorylated Rb in NK cells isolated from the healthy donors and cancer patients.

Abnormal Expression of c-Myc Oncogene in NK Cells in Patients with Cancer.

Natural killer (NK) cells have received a lot of attention in recent years for the roles they play in immunity and particularly in antitumor immune responses. Although defects in NK cell functions are recognized as important mechanisms for immune evasion of malignant cells, molecular pathways regulating NK cell dysfunction and exhaustion in cancer are largely unknown. Here we tested whether the c-myc proto-oncogene, known to promote cell proliferation, growth, differentiation, and apoptosis by regulating the expression of numerous target genes, may be involved in the mechanism of NK cell abnormalities in patients with lung and gastric cancer.

Oncogenes in immune cells as potential therapeutic targets.

The role of deregulated expression of oncogenes and tumor-suppressor genes in tumor development has been intensively investigated for decades. However, expression of oncogenes and their potential role in immune cell defects during carcinogenesis and tumor progression have not been thoroughly assessed. The defects in proto-oncogenes have been well documented and evaluated mostly in tumor cells, despite the fact that proto-oncogenes are expressed in all cells, including cells of the immune system.

Alterations of oncogenes expression in NK cells in patients with cancer.

Introduction: C-kit/SCF signaling plays a key role in regulating NK cell homeostasis, maturation, proliferation, and cytotoxicity. C-kit-deficiency in NK cells results in significant reduction of their number, suggesting an imperative role for c-kit signaling in NK cell biology. We have recently showed that human NK cells express not only c-kit-receptor, but also both membrane-bound and soluble forms of c-kit ligand-Stem cell factor.