학술논문
ACKR4 restrains antitumor immunity by regulating CCL21.
Document Type
Article
Author
Whyte, Carly E; Osman, Maleika; Kara, Ervin E; Abbott, Caitlin; Foeng, Jade; McKenzie, Duncan R; Fenix, Kevin A; Harata-Lee, Yuka; Foyle, Kerrie L; Boyle, Sarah T; Kochetkova, Marina; Aguilera, Amelia Roman; Hou, Jiajie; Li, Xian-Yang; Armstrong, Mark A; Pederson, Stephen M; Comerford, Iain; Smyth, Mark J; McColl, Shaun R
Source
The Journal of Experimental Medicine; June 2020, Vol. 217 Issue: 6 pe20190634-e20190634, 1p
Subject
Language
ISSN
00221007; 15409538
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.