Suppression of intratumoral CCL22 by type i interferon inhibits migration of regulatory T cells and blocks cancer progression

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 activ...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2015-11, Vol.75 (21), p.4483-4493
Main Authors: Anz, David, Rapp, Moritz, Eiber, Stephan, Koelzer, Viktor H, Thaler, Raffael, Haubner, Sascha, Knott, Max, Nagel, Sarah, Golic, Michaela, Wiedemann, Gabriela M, Bauernfeind, Franz, Wurzenberger, Cornelia, Hornung, Veit, Scholz, Christoph, Mayr, Doris, Rothenfusser, Simon, Endres, Stefan, Bourquin, Carole
Format: Article
Language:English
Subjects:
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
Macrophages - immunology
MCF-7 Cells
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
T-Lymphocytes, Regulatory - immunology
T-Lymphocytes, Regulatory - transplantation
Tumor Escape - immunology
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Summary: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.
ISSN:0008-5472
1538-7445
DOI:10.1158/0008-5472.CAN-14-3499