Role of natural killer cells in isocitrate dehydrogenase 1/2 mutant glioma pathogenesis and emerging therapies

Gliomas are the most common primary central nervous system malignancy and have an overall poor prognosis, despite aggressive treatment. Understanding the immune microenvironment of these fatal tumors will advance discovery of immune-related therapeutic targets. Natural killer (NK) cells are innate lymphoid cells that constitute the first line of host-tumor immune responses since these cells do not require prior sensitization or tumor antigen recognition to kill. NK cells kill tumor cells by recognizing stress-induced ligands expressed on tumor cells, thereby providing an efficient path to early tumor cytolysis. Dysregulation of NK-mediated immunity plays a prominent role in immune escape for glioblastoma (World Health Organization Grade IV gliomas) and for various low-grade diffuse gliomas. Thus, the biology of NK cells is fertile ground for identifying novel immunotherapeutic targets in glioma. This review discusses the biology of NK cells as well as the potential applications for immunotherapy in the treatment of gliomas.