NK Cells in the Tumor Microenvironment

Natural killer cells are powerful effectors of innate immunity that constitute a first line of defense against cancer. NK cells express an array of germline-encoded receptors which allow them to eliminate transformed cells and spare normal, healthy cells. Owing to their ability to kill circulating tumor cells, NK cells play a major role in the protection against cancer metastases. There is also convincing evidence that NK cells protect against some hematological cancers such as acute myeloid leukemia. However, the importance of NK cells for the control of established solid tumors is rather uncertain. Several mechanisms impede NK cell-mediated elimination of solid tumors, starting with the incapacity of NK cells to infiltrate the core of the tumor. In addition, immune escape mechanisms are at play in both solid and hematological cancers. These include the immunoediting of tumor cells and aberrant chronic inflammation that renders NK cells ineffective. In this chapter, I review the phenotypic characteristics of NK cells within the tumor microenvironment. Furthermore, I describe the mechanisms by which NK cells contribute to antitumor immunity. Finally, I review the different immune-evasion factors that impair NK cell activity against cancer.