Abstract |
The chemokine CCL22 is abundantly expressed in many types of cancer and is instrumental for intratumoral recruitment of regulatory T cells (Treg), an important subset of immunosuppressive and tumor-promoting lymphocytes. In this study, we offer evidence for a generalized strategy to blunt Treg activity that can limit immune escape and promote tumor rejection. Activation of innate immunity with Toll-like receptor (TLR) or RIG-I-like receptor (RLR) ligands prevented accumulation of Treg in tumors by blocking their immigration. Mechanistic investigations indicated that Treg blockade was a consequence of reduced intratumoral CCL22 levels caused by type I IFN. Notably, stable expression of CCL22 abrogated the antitumor effects of treatment with RLR or TLR ligands. Taken together, our findings argue that type I IFN blocks the Treg-attracting chemokine CCL22 and thus helps limit the recruitment of Treg to tumors, a finding with implications for cancer immunotherapy.
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Authors | David Anz, Moritz Rapp, Stephan Eiber, Viktor H Koelzer, Raffael Thaler, Sascha Haubner, Max Knott, Sarah Nagel, Michaela Golic, Gabriela M Wiedemann, Franz Bauernfeind, Cornelia Wurzenberger, Veit Hornung, Christoph Scholz, Doris Mayr, Simon Rothenfusser, Stefan Endres, Carole Bourquin |
Journal | Cancer research
(Cancer Res)
Vol. 75
Issue 21
Pg. 4483-93
(Nov 01 2015)
ISSN: 1538-7445 [Electronic] United States |
PMID | 26432403
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | ©2015 American Association for Cancer Research. |
Chemical References |
- CCL22 protein, human
- Chemokine CCL22
- Interferon Type I
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Topics |
- Adoptive Transfer
- Animals
- Cell Line, Tumor
- Cell Movement
(immunology)
- Chemokine CCL22
(metabolism)
- Dendritic Cells
(immunology)
- Disease Progression
- Female
- Humans
- Immunity, Innate
(immunology)
- Interferon Type I
(immunology)
- Jurkat Cells
- Lymphocyte Activation
(immunology)
- MCF-7 Cells
- Macrophages
(immunology)
- Mice
- Mice, Inbred BALB C
- Mice, Inbred C57BL
- T-Lymphocytes, Regulatory
(immunology, transplantation)
- Tumor Escape
(immunology)
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