Natural killer cells control metastasis via structural editing of primary tumors in mice

  • Batya Isaacson
  • Ofer MandelboimEmail author
Focussed Research Review


Natural killer (NK) cells are innate immune lymphocytes which express an array of activating and inhibitory receptors. These receptors bind a large spectrum of ligands, which are expressed on stressed, malignantly transformed or virally infected cells, as well as on bacterial, fungal, and parasitic pathogens. The decision on whether or not to kill the target is based on the integration of activating and inhibitory signals sent downstream from NK cell receptors. One of the most prominent NK cell activating receptor families is the family of natural cytotoxicity receptors (NCRs) which includes NKp30, NKp44, and NKp46. NKp46 is the only NCR to have a fully functional mouse orthologue denoted Ncr1. Despite a large body of evidence highlighting its importance in the clearance of both solid and liquid tumors, the membrane-bound tumor ligand for NKp46 and its mouse orthologue Ncr1 is still unknown. Here we review the discovery of a novel role for NKp46/Ncr1, not only in tumor clearance but also in prevention of metastasis by structural editing of primary tumors.


NK cells NKp46 Ncr1 IFNγ FN1 TIMO2018 





Interferon gamma


Knock out


Major histocompatibility complex


Natural cytotoxicity receptor


Natural killer


Reflectance confocal microscopy


Tumor necrosis factor alpha


Author contributions

Batya Isaacson wrote the first draft and Ofer Mandelboim edited the manuscript. Both authors revised the manuscript and approved the final version of this paper.


This work was supported by the Israel Science Foundation (Moked grant and Israel-China grant), the German-Israeli Foundation for Scientific Research and Development (GIF), the Israel Cancer Research Fund (ICRF) professorship grant, and the Ministry of Science and Technology grant (all to Ofer Mandelboim.).

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interests.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.The Concern Foundation Laboratories at the Lautenberg Center for Immunology and Cancer Research, The Hebrew University Medical SchoolIMRICJerusalemIsrael

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