ASPECTS OF NATURAL-KILLER-CELL SURVEILLANCE AND THERAPY OF CANCER Mark J. Smyth, Yoshihiro Hayakawa, Kazuyoshi Takeda & Hideo Yagita Preface Natural-killer (NK) cells form a first line of defence against pathogens or host cells that are stressed and/or cancerous. NK cells express surface receptors that receive signals from the environment and determine their response to foreign or malignant cells. NK cells respond to these signals by producing effector molecules that can both directly suppress tumour growth and convey important information to the rest of the immune system. We have only recently begun to appreciate the potential for NK cells to be rationally manipulated in the treatment of human cancers. Summary Natural-killer (NK) cells are important components of the innate immune system. There is evidence of tumour rejection by NK cells. NK cells act against tumour initiation, growth and metastasis in rodents and humans. NK cells suppress tumour cells though a variety of effector mechanisms, including the perforin/granzyme-containing granule-mediated pathway, death-receptor pathway and IFN--mediated pathway. NK-cell functions are regulated by the balance of inhibitory and activating signals that they receive through their various classes of receptor. Each class and functional role in controlling tumour immunity is discussed. Co-stimulatory molecules that are expressed by NK cells further serve to control NK-cell antitumour function and evoke subsequent adaptive T-cell immunity. The cytokine and chemokine environment serves to define the differentiation, proliferation and recruitment of NK cells. NK cells might influence the development of adaptive immunity through cross-talk with antigen-presenting dendritic cells. The clinical use of NK cells in patients has undergone 15 years of refinement. With the description of key developmental factors for NK cells and the definition of immunoglobulin-like receptors for MHC class I, more sophisticated approaches to NK-cell transfer are yielding impressive antitumour responses. Nature Reviews Cancer 2, 850 -861 (2002) Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. Support our work with any size DONATION - see left side of any page - for how to donate. You can help raise awareness of CAM.