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

Cancer Res. 2015 Nov 1;75(21):4483-93. doi: 10.1158/0008-5472.CAN-14-3499. Epub 2015 Oct 2.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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*
  • T-Lymphocytes, Regulatory / transplantation
  • Tumor Escape / immunology


  • CCL22 protein, human
  • Chemokine CCL22
  • Interferon Type I