ACKR4 restrains antitumor immunity by regulating CCL21
Open Access
- 14 April 2020
- journal article
- research article
- Published by Rockefeller University Press in The Journal of Experimental Medicine
- Vol. 217 (6)
- https://doi.org/10.1084/jem.20190634
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
Funding Information
- National Health and Medical Research Council (1030247, 1105312)
- National Health and Medical Research Council (1132519, 1078671, 1173958)
- Tizona Therapeutics
- Carina Biotech
- Bristol-Myers Squibb
- Aduro Biotech
- Tizona Therapeutics
- Tizona Therapeutics
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