Cancer-associated Molecular Abnormalities in Human NK cells

Abstract

Natural Killer (NK) cells play a key role in the immune responses against infection and cancer as powerful cytotoxic effector cells and regulators of both innate and adaptive immunity [1,2]. Therefore, defects in NK cell functions are important mechanisms for immune evasion of malignant cells [3]. For instance, the ability of tumor cells and tumor-associated stromal/infiltrating cells to inhibit NK cell activity, which results in preventing NK cells from recognizing and killing tumor cells, has been reported for melanoma, neuroblastoma, gastrointestinal sarcoma, hepatocellular cancer (HCC), pancreatic cancer, colorectal carcinoma and other types of cancer [4-9]. A potential loss of NK cell numbers and function at preneoplastic stages of tumorigenesis as a possible mechanism for cancer induction and progression has been also recently proposed [5,10]. However, molecular mechanisms regulating NK cell dysfunction and exhaustion in cancer are largely unclear.