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

The Journal of Immunology : Official Journal of the American Association of Immunologists
Christopher A HansellGerard J Graham

Abstract

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.

References

Mar 1, 1983·Proceedings of the National Academy of Sciences of the United States of America·S C Wright, B Bonavida
Jun 4, 1999·Immunology Today·A Mantovani
Mar 23, 2004·Annual Review of Immunology·Antal Rot, Ulrich H von Andrian
Apr 7, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Raffaella BonecchiAlberto Mantovani
Mar 8, 2005·Nature Immunology·Thomas JamiesonGerard J Graham
Jul 4, 2007·The Journal of Clinical Investigation·Robert J B NibbsGerard J Graham
Aug 21, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Clive S McKimmieGerard J Graham
Mar 13, 2009·Nature Reviews. Cancer·Johanna A Joyce, Jeffrey W Pollard
Mar 21, 2009·Nature Protocols·Robert H KutnerJakob Reiser
Mar 25, 2009·Nature Reviews. Cancer·Christoph A Klein
Oct 19, 2010·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Xing LuYan-Qun Xiang
Apr 16, 2011·Nature Reviews. Immunology·Thomas J Schall, Amanda E I Proudfoot
Jun 10, 2011·Nature·Bin-Zhi QianJeffrey W Pollard
Oct 13, 2011·The Journal of Pathology·Frances R Balkwill
Nov 1, 2011·The American Journal of Pathology·Yuko NakasoneMinoru Hasegawa
Nov 6, 2012·The Journal of Pathology·Gerard J Graham, Massimo Locati
Apr 30, 2013·Methods in Molecular Biology·Laura B FordRobert J B Nibbs
Jun 19, 2013·PloS One·Zuhair K BallasMichael R Shey
Dec 10, 2013·Nature Reviews. Immunology·Robert J B Nibbs, Gerard J Graham
Feb 20, 2014·Nature Immunology·Françoise BachelerieMarcus Thelen
May 23, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Michelle L Le BrocqGerard J Graham
Jun 4, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Laura B FordRobert J B Nibbs
Jan 16, 2015·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Josh M MorgantiSusanna Rosi
Oct 28, 2015·The Journal of Experimental Medicine·Mary J van HeldenThierry Walzer
Feb 16, 2018·Nature Communications·Matteo MassaraRaffaella Bonecchi

❮ Previous
Next ❯

Citations

Dec 29, 2018·International Journal of Molecular Sciences·Elisabetta MarcuzziBianca Calì
Jun 26, 2020·Frontiers in Immunology·Dina MoreinAdit Ben-Baruch
Mar 22, 2019·Frontiers in Immunology·Valeria Mollica PoetaRaffaella Bonecchi
May 28, 2020·International Journal of Molecular Sciences·Magdalena GroblewskaBarbara Mroczko
Dec 2, 2020·International Reviews of Immunology·Elaheh ArianfarAli Memarian
Apr 7, 2019·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Qian ZhangShengtao Zhou
Dec 6, 2020·Cancer Discovery·Beatriz CózarEric Vivier
Mar 29, 2019·Redox Biology·Sin Yee GunSiew Cheng Wong
Apr 4, 2021·Cancers·Andy ChevignéMartyna Szpakowska
Aug 31, 2021·Clinical and Translational Medicine·Qian HaoXiang Zhou

❮ Previous
Next ❯

Methods Mentioned

BETA
FACS
flow cytometry
Fluorescence
PCR

Software Mentioned

Primer3
GraphPad Prism
Zeiss ZEN
AxioVision

Related Concepts

Related Feeds

Cancer Biology: Molecular Imaging

Molecular imaging enables noninvasive imaging of key molecules that are crucial to tumor biology. Discover the latest research in molecular imaging in cancer biology in this feed.