Role of IL-13 in regulation of anti-tumor immunity and tumor growth.
Major mediators of anti-tumor immunity are CD4(+) T(h)1 cells and CD8(+) cytotoxic T lymphocytes (CTLs). In tumor-bearing animals, the T(h)1- and CTL-mediated anti-tumor immunity is down-regulated in multiple ways. Better understanding of negative regulatory pathways of tumor immunity is crucial for the development of anti-tumor vaccines and immunotherapies. Since immune deviation toward T(h)2 suppresses T(h)1 development, it has been thought that induction affecting a T(h)2 immune response is one of the mechanisms that down-regulate effective tumor immune responses. Recent studies using T(h)2-deficient signal transducer and activator (Stat6) KO mice demonstrated that this hypothesis was the case. IL-13 is one of the T(h)2 cytokines that has very similar features to IL-4 through sharing some receptor components and Stat6 signal transduction. It has been thought that IL-13 is not as critical for immune deviation as IL-4 since it cannot directly act on T cells. However, recent studies of IL-13 reveal that this cytokine plays a critical role in many aspects of immune regulation. Studies from our lab and others indicate that IL-13 is central to a novel immunoregulatory pathway in which NKT cells suppress tumor immunosurveillance. Here we will describe biological properties and functions of IL-13, its role in the negative regulation of anti-tumor immunity, and effects of IL-13 on tumor cells themselves.
Terabe
Masaki
M
Molecular Immunogenetics and Vaccine Research Section, Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1578, USA. terabe@mail.nih.gov
Park
Jong Myun
JM
Berzofsky
Jay A
JA
D000818:Animals; D015551:Autoimmunity; D015704:CD4 Antigens / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance; D007157:Immunologic Surveillance; D018793:Interleukin-13 / Q000502:physiology*; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D019948:Receptors, Interleukin-4 / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*
D015704:CD4 Antigens; D018793:Interleukin-13; D019948:Receptors, Interleukin-4