IL-6-mediated environmental conditioning of defective Th1 differentiation dampens antitumour immune responses in old age

Nat Commun. 2015 Apr 7;6:6702. doi: 10.1038/ncomms7702.

Abstract

Decline in immune function and inflammation concomitantly develop with ageing. Here we focus on the impact of this inflammatory environment on T cells, and demonstrate that in contrast to successful tumour elimination in young mice, replenishment of tumour-specific CD4(+) T cells fails to induce tumour regression in aged hosts. The impaired antitumour effect of CD4(+) T cells with their defective Th1 differentiation in an aged environment is restored by interleukin (IL)-6 blockade or IL-6 deficiency. IL-6 blockade also restores the impaired ability of CD4(+) T cells to promote CD8(+) T-cell-dependent tumour elimination in aged mice, which requires IFN-γ. Furthermore, IL-6-stimulated production of IL-4/IL-21 through c-Maf induction is responsible for impaired Th1 differentiation. IL-6 also contributes to IL-10 production from CD4(+) T cells in aged mice, causing attenuated responses of CD8(+) T cells. These findings suggest that IL-6 serves as an extrinsic factor counteracting CD4(+) T-cell-mediated immunity against tumour in old age.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / immunology*
  • Animals
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Differentiation / immunology*
  • Fibrosarcoma / immunology*
  • Immunity, Cellular / immunology
  • Interferon-gamma / immunology
  • Interleukin-10 / immunology
  • Interleukin-4 / immunology
  • Interleukin-6 / immunology*
  • Interleukins / immunology
  • Mice
  • Mice, Inbred C57BL
  • Neoplasm Transplantation
  • Proto-Oncogene Proteins c-maf / immunology
  • Th1 Cells / immunology*
  • Tumor Escape

Substances

  • IL10 protein, mouse
  • Interleukin-6
  • Interleukins
  • Maf protein, mouse
  • Proto-Oncogene Proteins c-maf
  • Interleukin-10
  • Interleukin-4
  • Interferon-gamma
  • interleukin-21