Natural Killing of Cancer Cells

Natural killer (NK) cells, part of the innate immune system, serve as the first line of defense against viral infections and cancer. However, under unclear conditions, NK cells can enter an "anergic" state, in which their function is impaired. Anergic NK cells fail to respond to threats, allowing pathogens and cancer cells to evade immune surveillance. In a study published in The EMBO Journal, Prof. Mira Barda-Saad and colleagues identified striking similarities between these anergic cells and tumor-infiltrating "exhausted" NK cells. Using transcriptomic, phenotypic, and functional analyses, the team showed that both states are regulated by the transcription factor Egr2 and the enzyme DGKα. Notably, silencing Egr2 expression using a nanoparticle-based miRNA delivery system successfully reprogrammed anergic NK cells to a functional state, both in 3D cell cultures and in in vivo tumor models. These findings reveal a shared molecular mechanism of NK cell dysfunction and suggest a novel approach to restore NK cell activity in tumors.