NK Cell-Based Immunotherapy

The debate has been raging for many years about the immune system’s ability to identify and destroy emerging tumor cells, and to thereby act as a barrier to cancer development. Investigators have now used both murine models and human studies to offer convincing evidence in support of this concept. Accumulating information about the particular effector molecules and immune cell types involved in this process has formed the basis for rational design of immunotherapies. Both T lymphocytes and Natural killer (NK) cells participate in cancer immune surveillance. Intricate effector mechanisms are involved in providing protection against both malignant and virally infected cells. Our vision of NK cells as therapeutic agents has evolved from the seminal discovery of inhibitory and activating NK receptors. NK cells can recognize tumor cells while preserving normal self, and the understanding of the mechanisms allowing for this preferential recognition pattern has greatly impacted the success of stem cell therapy and immunotherapy. Two main strategies are used by NK cells to recognize tumor targets. A number of tumor cells down-regulate major histocompatibility complex (MHC) class I molecules, protecting against T-cell recognition but releasing the inhibitory breaks in NK cells. The balance of activating and inhibitory NK receptor signals determines whether nascent tumor cells will be recognized and destroyed. In this chapter, the concepts of immune surveillance, immunoediting and NK immunotherapy are discussed. Effective NK immunotherapy may become a reality for many types of cancers in the near future.