The Atypical Chemokine Receptor Ackr2 Constrains NK Cell Migratory Activity and Promotes Metastasis

J Immunol. 2018 Oct 15;201(8):2510-2519. doi: 10.4049/jimmunol.1800131. Epub 2018 Aug 29.


Chemokines have been shown to be essential players in a range of cancer contexts. In this study, we demonstrate that mice deficient in the atypical chemokine receptor Ackr2 display impaired development of metastasis in vivo in both cell line and spontaneous models. Further analysis reveals that this relates to increased expression of the chemokine receptor CCR2, specifically by KLRG1+ NK cells from the Ackr2-/- mice. This leads to increased recruitment of KLRG1+ NK cells to CCL2-expressing tumors and enhanced tumor killing. Together, these data indicate that Ackr2 limits the expression of CCR2 on NK cells and restricts their tumoricidal activity. Our data have important implications for our understanding of the roles for chemokines in the metastatic process and highlight Ackr2 and CCR2 as potentially manipulable therapeutic targets in metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Lewis Lung
  • Cell Movement
  • Chemokine CCL2 / metabolism
  • Cytotoxicity, Immunologic
  • Killer Cells, Natural / immunology*
  • Lectins, C-Type
  • Melanoma, Experimental
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neoplasm Metastasis
  • Neoplasms, Experimental / immunology*
  • Receptors, CCR2 / metabolism
  • Receptors, Chemokine / genetics
  • Receptors, Chemokine / metabolism*
  • Receptors, Immunologic / metabolism


  • Ackr2 protein, mouse
  • Ccr2 protein, mouse
  • Chemokine CCL2
  • Klrg1 protein, mouse
  • Lectins, C-Type
  • Receptors, CCR2
  • Receptors, Chemokine
  • Receptors, Immunologic