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Suppression of Intratumoral CCL22 by Type I Interferon Inhibits Migration of Regulatory T Cells and Blocks Cancer Progression

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author 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,
Project RLR/TLR combination therapy: Mechanisms of T-cell recruitment into gastric tumors
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Original article (peer-reviewed)

Journal Cancer Research
Volume (Issue) 75(21)
Page(s) 4483 - 4493
Title of proceedings Cancer Research
DOI 10.1158/0008-5472.can-14-3499

Open Access

URL http://cancerres.aacrjournals.org/content/75/21/4483.long
Type of Open Access Publisher (Gold Open Access)

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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