ACKR4 restrains antitumor immunity by regulating CCL21.

Autor:	Whyte CE; Chemokine Biology Laboratory, Department of Molecular and Biomedical Science, School of Biological Sciences, The University of Adelaide, Adelaide, South Australia, Australia., Osman M; Chemokine Biology Laboratory, Department of Molecular and Biomedical Science, School of Biological Sciences, The University of Adelaide, Adelaide, South Australia, Australia., Kara EE; Chemokine Biology Laboratory, Department of Molecular and Biomedical Science, School of Biological Sciences, The University of Adelaide, Adelaide, South Australia, Australia., Abbott C; Chemokine Biology Laboratory, Department of Molecular and Biomedical Science, School of Biological Sciences, The University of Adelaide, Adelaide, South Australia, Australia., Foeng J; Chemokine Biology Laboratory, Department of Molecular and Biomedical Science, School of Biological Sciences, The University of Adelaide, Adelaide, South Australia, Australia., McKenzie DR; Chemokine Biology Laboratory, Department of Molecular and Biomedical Science, School of Biological Sciences, The University of Adelaide, Adelaide, South Australia, Australia., Fenix KA; Chemokine Biology Laboratory, Department of Molecular and Biomedical Science, School of Biological Sciences, The University of Adelaide, Adelaide, South Australia, Australia., Harata-Lee Y; Chemokine Biology Laboratory, Department of Molecular and Biomedical Science, School of Biological Sciences, The University of Adelaide, Adelaide, South Australia, Australia., Foyle KL; Chemokine Biology Laboratory, Department of Molecular and Biomedical Science, School of Biological Sciences, The University of Adelaide, Adelaide, South Australia, Australia., Boyle ST; Centre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, South Australia, Australia., Kochetkova M; Centre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, South Australia, Australia., Aguilera AR; Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia., Hou J; Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia., Li XY; Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia., Armstrong MA; Bioinformatics Hub, School of Biological Sciences, The University of Adelaide, Adelaide, South Australia, Australia., Pederson SM; Bioinformatics Hub, School of Biological Sciences, The University of Adelaide, Adelaide, South Australia, Australia., Comerford I; Chemokine Biology Laboratory, Department of Molecular and Biomedical Science, School of Biological Sciences, The University of Adelaide, Adelaide, South Australia, Australia., Smyth MJ; Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia., McColl SR; Chemokine Biology Laboratory, Department of Molecular and Biomedical Science, School of Biological Sciences, The University of Adelaide, Adelaide, South Australia, Australia.
Jazyk:	angličtina
Zdroj:	The Journal of experimental medicine [J Exp Med] 2020 Jun 01; Vol. 217 (6).
DOI:	10.1084/jem.20190634
Abstrakt:	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. Competing Interests: Disclosures: Dr. Harata-Lee reported a patent number 2012903874 with royalties paid, "Tizona Therapeutics." Dr. Comerford reported a patent number 2012903874 with royalties paid, "Tizona Therapeutics." Dr. Smyth reported grants from Bristol Meyers Squibb, grants from Tizona Therapeutics, grants from Aduro Biotech, personal fees from Tizona Therapeutics, and personal fees from Compass Therapeutics outside the submitted work. In addition, Dr. Smyth had a patent number 2012903874 issued. Dr. McColl reported grants from Tizona Therapeutics, personal fees from Tizona Therapeutics, and grants from Carina Biotech outside the submitted work. In addition, Dr. McColl had a patent number 2012903874 with royalties paid, "Tizona Therapeutics." No other disclosures were reported. (© 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.)
Databáze:	MEDLINE
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