1. Suppression of intratumoral CCL22 by type i interferon inhibits migration of regulatory T cells and blocks cancer progression
- Author
-
Michaela Golic, Veit Hornung, Sarah Nagel, Simon Rothenfusser, Max M. L. Knott, Franz Bauernfeind, Viktor H. Koelzer, Stephan Eiber, Stefan Endres, Carole Bourquin, Raffael Thaler, Sascha Haubner, Cornelia Wurzenberger, Gabriela M. Wiedemann, David Anz, Doris Mayr, Christoph Scholz, and Moritz Rapp
- Subjects
Cancer Research ,Adoptive cell transfer ,medicine.medical_treatment ,chemical and pharmacologic phenomena ,Biology ,Lymphocyte Activation ,Jurkat cells ,T-Lymphocytes, Regulatory ,Jurkat Cells ,Mice ,Immune system ,Cancer immunotherapy ,Interferon ,Cell Movement ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Chemokine CCL22 ,Mice, Inbred BALB C ,Macrophages ,Dendritic Cells ,Adoptive Transfer ,Immunity, Innate ,Mice, Inbred C57BL ,Oncology ,Tumor Escape ,Immunology ,Interferon Type I ,Disease Progression ,MCF-7 Cells ,Female ,Interferon type I ,CCL22 ,medicine.drug - 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. Cancer Res; 75(21); 4483–93. ©2015 AACR.
- Published
- 2014