Natural killer cells for osteosarcoma

Natural killer (NK) cells are lymphocytes of the innate immune system that have the ability to recognize malignant cells through detection of a variety of cell-surface indicators of stress and danger. Once activated through such recognition, NK cells release cytokines and induce target cell lysis through a variety of mechanisms. NK cells are increasingly recognized as important mediators of other immu-notherapeutic modalities, including cytokines, antibodies, immunomodulators, and stem cell transplantation. Adoptive immunotherapies with NK cells are being tested in early-stage clinical trials, and recent advances in manipulating their number and function have caused a renewed emphasis on this cancer-fi ghting cell. In this chapter we address the evidence for NK cell recognition of osteosarcoma in vitro and in vivo, discuss new therapies that are directly or indirectly dependent on NK cell function, and describe potential approaches for manipulating NK cell number and function to enhance therapy against osteosarcoma.