Natural Killer Cell Immunotherapy for Osteosarcoma.

Natural killer (NK) cells are lymphocytes of the innate immune system that have the ability to recognize malignant cells through balanced recognition of cell-surface indicators of stress and danger. Once activated through such recognition, NK cells release cytokines and induce target cell lysis through multiple mechanisms. NK cells are increasingly recognized for their role in controlling tumor progression and metastasis and as important mediators of immunotherapeutic modalities such as cytokines, antibodies, immunomodulating drugs, and stem cell transplantation. Recent advances in manipulating NK cell number, function, and genetic modification have caused renewed interest in their potential for adoptive immunotherapies, which are actively being tested in clinical trials. Here, we summarize the evidence for NK cell recognition of osteosarcoma, discuss immune 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.