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Type: Journal article
Title: ACKR4 restrains antitumor immunity by regulating CCL21
Author: Whyte, C.E.
Osman, M.
Kara, E.E.
Abbott, C.
Foeng, J.
McKenzie, D.R.
Fenix, K.A.
Harata-Lee, Y.
Foyle, K.L.
Boyle, S.T.
Kochetkova, M.
Aguilera, A.R.
Hou, J.
Li, X.-Y.
Armstrong, M.A.
Pederson, S.M.
Comerford, I.
Smyth, M.J.
McColl, S.R.
Citation: Journal of Experimental Medicine, 2020; 217(6):1-S4
Publisher: Rockefeller University Press
Issue Date: 2020
ISSN: 0022-1007
Statement of
Carly E. Whyte, Maleika Osman, Ervin E. Kara, Caitlin Abbott, Jade Foeng, Duncan R. McKenzie, Kevin A. Fenix, Yuka Harata-Lee, Kerrie L. Foyle, Sarah T. Boyle, Marina Kochetkova, Amelia Roman Aguilera, Jiajie Hou, Xian-Yang Li, Mark A. Armstrong, Stephen M. Pederson, Iain Comerford, Mark J. Smyth, and Shaun R. McColl
Abstract: Current immunotherapies involving CD8⁺ T cell responses show remarkable promise, but their efficacy in many solid tumors is limited, in part due to the low frequency of tumor-specific T cells in the tumor microenvironment (TME). Here, we identified a role for host atypical chemokine receptor 4 (ACKR4) in controlling intratumor T cell accumulation and activation. In the absence of ACKR4, an increase in intratumor CD8⁺ T cells inhibited tumor growth, and nonhematopoietic ACKR4 expression was critical. We show that ACKR4 inhibited CD103⁺ dendritic cell retention in tumors through regulation of the intratumor abundance of CCL21. In addition, preclinical studies indicate that ACKR4 and CCL21 are potential therapeutic targets to enhance responsiveness to immune checkpoint blockade or T cell costimulation.
Keywords: Dendritic Cells
CD8-Positive T-Lymphocytes
Stromal Cells
Mice, Inbred C57BL
Neoplasm Metastasis
Disease Models, Animal
Integrin alpha Chains
Antigens, CD
Survival Analysis
Cell Proliferation
Receptors, CCR
Chemokine CCL21
Immune Checkpoint Inhibitors
Rights: © 2020 Crown copyright. The government of Australia, Canada, or the UK ("the Crown") owns the copyright interests of authors who are government employees. The Crown Copyright is not transferable. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at
DOI: 10.1084/jem.20190634
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Appears in Collections:Aurora harvest 4
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