Enrichment of Foxp3+ CD4 regulatory T cells in migrated T cells to IL-6- and IL-8-expressing tumors through predominant induction of CXCR1 by IL-6

J Immunol. 2010 Dec 1;185(11):6734-40. doi: 10.4049/jimmunol.1000225. Epub 2010 Nov 3.

Abstract

Analysis of cytokine and chemokine production by tumor cell lines including five lung cancers, a malignant mesothelioma, and a malignant melanoma recently established in our laboratory showed rather high production of IL-8 in all tumors and IL-6 in one lung cancer, the malignant mesothelioma, and the malignant melanoma. We investigated the migration of PBMCs to these tumor cells using Transwell plates and showed enrichment of Foxp3(+) CD4 regulatory T cells (Tregs) in migrated T cells to both IL-6- and IL-8-producing tumors. Marked induction of CXCR1 expression on Foxp3(+) CD4 Tregs by IL-6 followed by IL-8-mediated migration appeared to be responsible for enriched migration. Frequent production of IL-8 by the tumors and Treg migration to those tumors through induction of IL-8R expression by IL-6 is one of the mechanisms for tumor escape.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / pathology
  • Cell Line, Tumor
  • Cell Movement / immunology*
  • Forkhead Transcription Factors / biosynthesis*
  • Humans
  • Interleukin-6 / biosynthesis*
  • Interleukin-6 / physiology
  • Interleukin-8 / biosynthesis*
  • Interleukin-8 / physiology
  • Lung Neoplasms / immunology
  • Lung Neoplasms / metabolism
  • Melanoma / immunology
  • Melanoma / metabolism
  • Mesothelioma / immunology
  • Mesothelioma / metabolism
  • Receptors, Interleukin-8A / biosynthesis*
  • Receptors, Interleukin-8A / physiology
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism*
  • T-Lymphocytes, Regulatory / pathology
  • Tumor Cells, Cultured
  • Tumor Escape / immunology

Substances

  • CXCL8 protein, human
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • IL6 protein, human
  • Interleukin-6
  • Interleukin-8
  • Receptors, Interleukin-8A