Cell Metab. https://doi.org/10.1016/j.cmet.2018/06.021 (2018)

Dysfunction of natural killer (NK) cells is linked to tumor progression. In Cell Metabolism, Wei and colleagues use a Kras-driven model of lung cancer in mice to show that induction of the glycolysis-inhibiting enzyme FBP1 in NK cells impairs their viability and gradually induces a dysfunctional state. NK cells potently prevent tumor initiation (stage 1) but fail to control the promotion or progression (stages 2 and 3) of lung cancer. Stage 2 and stage 3 NK cells have attenuated cytotoxicity and proliferation, increased expression of intracellular ROS and FBP1 and decreased glycolysis, relative to that of spleen NK cells, but stage 1 NK cells do not. Inhibition of FBP1 ‘rescues’ the cytotoxicity, viability and proliferation of stage 2 NK cells, but not that of stage 3 NK cells, and, after transfer of stage 2 NK cells into these mice, slows tumor growth.