Immunity 48, 107–119 (2018)

The presence of natural killer (NK) cells in tumors correlates with a better prognosis. In Immunity, Glasner et al. show that secretion of interferon-γ (IFN-γ) by intratumoral NK cells after signaling via the NK cell receptor NKp46 (in humans) or Ncr1 (in mice) alters tumor architecture through induction of the extracellular matrix protein fibronectin1. Ncr1-deficient mice have less production of IFN-γ from intratumoral NK cells and worse tumor architecture and develop more metastases. Fibronectin1 is strongly induced in tumor cells by IFN-γ signaling, and its knockdown results in more-aggressive tumors. Treatment with recombinant IFN-γ or overexpression of Ncr1 in NK cells results in fewer metastases. In humans, expression of NKp46, IFN-γ, the IFN-γ receptor and fibronectin1 correlates with improved survival.