Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/126382
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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):1-11
Publisher: Rockefeller University Press
Issue Date: 2020
ISSN: 0022-1007
1540-9538
Statement of
Responsibility: 
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; Animals; Mice, Inbred C57BL; Humans; Neoplasms; Neoplasm Metastasis; Disease Models, Animal; Integrin alpha Chains; Antigens, CD; Survival Analysis; Cell Proliferation; Immunity; 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 http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
RMID: 1000021424
DOI: 10.1084/jem.20190634
Grant ID: http://purl.org/au-research/grants/nhmrc/1030247
http://purl.org/au-research/grants/nhmrc/1105312
http://purl.org/au-research/grants/nhmrc/1132519
http://purl.org/au-research/grants/nhmrc/1078671
http://purl.org/au-research/grants/nhmrc/1173958
Appears in Collections:Medicine publications

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