The atypical chemokine receptor Ackr2 constrains NK cell migratory activity and promotes metastasis

Hansell, C. A.H. et al. (2018) The atypical chemokine receptor Ackr2 constrains NK cell migratory activity and promotes metastasis. Journal of Immunology, 201(8), pp. 2510-2519. (doi:10.4049/jimmunol.1800131) (PMID:30158126)

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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.

Item Type:Articles
Additional Information:This work was supported by a program grant from the Medical Research Council and a Wellcome Trust Senior Investigator Award. G.J.G. is a recipient of a Wolfson Royal Society Research Merit Award. The study benefited from a generous contribution from the White Feather Appeal and Wellcome Trust Institutional Strategic Support Fund Grant 097821/Z/11/Z.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Burgoyne, Paul and Fraser, Dr Alasdair and Hansell, Dr Chris and Macleod, Dr Megan and Nibbs, Professor Robert and Hayes, Mr Alan and Pingen, Dr Marieke and Wilson, Dr Gillian and Lee, Miss Kit and Medina-Ruiz, Dr Laura and Graham, Professor Gerard and Brownlie, Ms Demi
Authors: Hansell, C. A.H., Fraser, A. R., Hayes, A. J., Pingen, M., Burt, C. L., Lee, K. M., Medina-Ruiz, L., Brownlie, D., Macleod, M. K.L., Burgoyne, P., Wilson, G. J., Nibbs, R. J.B., and Graham, G. J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Journal of Immunology
Publisher:American Association of Immunologists
ISSN:0022-1767
ISSN (Online):1550-6606
Published Online:29 August 2018
Copyright Holders:Copyright © 2018 The Authors
First Published:First published in Journal of Immunology 201(8):2510-2519
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
681091The ACKR2-CCR2 axis in development and diseaseGerard GrahamMedical Research Council (MRC)MR/M019764/1III -IMMUNOLOGY
600961Dissecting the chemokine basis for the orchestration of the in vivo inflammatory responseGerard GrahamWellcome Trust (WELLCOTR)099251/Z/12/ZIII -IMMUNOLOGY