ACKR4 restrains antitumor immunity by regulating CCL21

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 (+7 others)
2020 Journal of Experimental Medicine   concern
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
more » ... cal. 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.
doi:10.1084/jem.20190634 pmid:32289156 pmcid:PMC7971131 fatcat:4u6ruodxdzghbkeut4aqlxyila