title: Inflammation driven by tumour-specific Th1 cells protects against B-cell cancer.
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.
authors.affiliation: Centre for Immune Regulation, Institute of Immunology, University of Oslo and Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors.forename: Ole Audun Werner
authors.initials: OA
authors.lastname: Haabeth
authors.forename: Kristina Berg
authors.initials: KB
authors.lastname: Lorvik
authors.forename: Clara
authors.initials: C
authors.lastname: Hammarström
authors.forename: Ian M
authors.initials: IM
authors.lastname: Donaldson
authors.forename: Guttorm
authors.initials: G
authors.lastname: Haraldsen
authors.forename: Bjarne
authors.initials: B
authors.lastname: Bogen
authors.forename: Alexandre
authors.initials: A
authors.lastname: Corthay
mesh_terms: D043165:Angiostatic Proteins / Q000096:biosynthesis / Q000276:immunology; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D045744:Cell Line, Tumor; D054357:Chemokine CXCL10 / Q000096:biosynthesis / Q000276:immunology; D054370:Chemokine CXCL9 / Q000096:biosynthesis / Q000276:immunology; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D018664:Interleukin-12 / Q000096:biosynthesis / Q000276:immunology; D053582:Interleukin-1alpha / Q000096:biosynthesis / Q000276:immunology; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000276:immunology; D007376:Interleukin-2 / Q000096:biosynthesis / Q000276:immunology; D015850:Interleukin-6 / Q000096:biosynthesis / Q000276:immunology; D016393:Lymphoma, B-Cell / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D009101:Multiple Myeloma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D059016:Tumor Microenvironment
chemical_list: D043165:Angiostatic Proteins; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D007376:Interleukin-2; D015850:Interleukin-6; D018664:Interleukin-12; D007371:Interferon-gamma