Immunotherapy represents one of the major breakthroughs in the treatment of cancer patients. Current therapies focus on harnessing the adaptive immune system, with great success achieved by interfering with immune checkpoints to unleash antitumor CD8+ T cell responses. There is emerging evidence that cancers develop multiple strategies to escape CD8+ T cell recognition. These tumors, however, can be preferentially attacked by natural killer (NK) cells. NK cells are innate lymphocytes that express activating receptors, including the NK group 2D (NKG2D) receptor, which recognize ligands displayed on the surface of tumor cells and pathogen-infected cells. On page 1537 of this issue, Ferrari de Andrade et al. (1) present an elegant approach to improve NK cell recognition of tumor cells, extending the range of immunotherapies beyond T cells.
