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