Inflammation driven by tumour-specific Th1 cells protects against B-cell cancer

Nat Commun. 2011;2:240. doi: 10.1038/ncomms1239.

Abstract

The immune system can both promote and suppress cancer. Chronic inflammation and proinflammatory cytokines such as interleukin (IL)-1 and IL-6 are considered to be tumour promoting. In contrast, the exact nature of protective antitumour immunity remains obscure. Here, we quantify locally secreted cytokines during primary immune responses against myeloma and B-cell lymphoma in mice. Strikingly, successful cancer immunosurveillance mediated by tumour-specific CD4(+) T cells is consistently associated with elevated local levels of both proinflammatory (IL-1α, IL-1β and IL-6) and T helper 1 (Th1)-associated cytokines (interferon-γ (IFN-γ), IL-2 and IL-12). Cancer eradication is achieved by a collaboration between tumour-specific Th1 cells and tumour-infiltrating, antigen-presenting macrophages. Th1 cells induce secretion of IL-1β and IL-6 by macrophages. Th1-derived IFN-γ is shown to render macrophages directly cytotoxic to cancer cells, and to induce macrophages to secrete the angiostatic chemokines CXCL9/MIG and CXCL10/IP-10. Thus, inflammation, when driven by tumour-specific Th1 cells, may prevent rather than promote cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiostatic Proteins / biosynthesis
  • Angiostatic Proteins / immunology
  • Animals
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Line, Tumor
  • Chemokine CXCL10 / biosynthesis
  • Chemokine CXCL10 / immunology
  • Chemokine CXCL9 / biosynthesis
  • Chemokine CXCL9 / immunology
  • Immunohistochemistry
  • Inflammation / immunology*
  • Inflammation / metabolism
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / immunology
  • Interleukin-12 / biosynthesis
  • Interleukin-12 / immunology
  • Interleukin-1alpha / biosynthesis
  • Interleukin-1alpha / immunology
  • Interleukin-1beta / biosynthesis
  • Interleukin-1beta / immunology
  • Interleukin-2 / biosynthesis
  • Interleukin-2 / immunology
  • Interleukin-6 / biosynthesis
  • Interleukin-6 / immunology
  • Lymphoma, B-Cell / immunology*
  • Lymphoma, B-Cell / metabolism
  • Lymphoma, B-Cell / pathology
  • Macrophages / cytology
  • Macrophages / immunology*
  • Macrophages / metabolism
  • Mice
  • Mice, SCID
  • Multiple Myeloma / immunology*
  • Multiple Myeloma / metabolism
  • Multiple Myeloma / pathology
  • Neoplasms / immunology*
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Signal Transduction
  • Th1 Cells / immunology
  • Th2 Cells / immunology
  • Tumor Microenvironment

Substances

  • Angiostatic Proteins
  • Chemokine CXCL10
  • Chemokine CXCL9
  • Interleukin-1alpha
  • Interleukin-1beta
  • Interleukin-2
  • Interleukin-6
  • Interleukin-12
  • Interferon-gamma

Associated data

  • GEO/GSE26912