title: Mathematical modeling of interleukin-27 induction of anti-tumor T cells response.
abstract: Interleukin-12 is a pro-inflammatory cytokine which promotes Th1 and cytotoxic T lymphocyte activities, such as Interferon-[Formula: see text] secretion. For this reason Interleukin-12 could be a powerful therapeutic agent for cancer treatment. However, Interleukin-12 is also excessively toxic. Interleukin-27 is an immunoregulatory cytokine from the Interleukin-12 family, but it is not as toxic as Interleukin-12. In recent years, Interleukin-27 has been considered as a potential anti-tumor agent. Recent experiments in vitro and in vivo have shown that cancer cells transfected with IL-27 activate CD8+ T cells to promote the secretion of anti-tumor cytokines Interleukin-10, although, at the same time, IL-27 inhibits the secretion of Interferon-[Formula: see text] by CD8+ T cells. In the present paper we develop a mathematical model based on these experimental results. The model involves a dynamic network which includes tumor cells, CD8+ T cells and cytokines Interleukin-27, Interleukin-10 and Interferon-[Formula: see text]. Simulations of the model show how Interleukin-27 promotes CD8+ T cells to secrete Interleukin-10 to inhibit tumor growth. On the other hand Interleukin-27 inhibits the secretion of Interferon-[Formula: see text] by CD8+ T cells which somewhat diminishes the inhibition of tumor growth. Our numerical results are in qualitative agreement with experimental data. We use the model to design protocols of IL-27 injections for the treatment of cancer and find that, for some special types of cancer, with a fixed total amount of drug, within a certain range, continuous injection has better efficacy than intermittent injections in reducing the tumor load while the treatment is ongoing, although the decrease in tumor load is only temporary.
authors.affiliation: Mathematical Biosciences Institute, The Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Kang-Ling
authors.initials: KL
authors.lastname: Liao
authors.affiliation: Department of Pathology and Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Xue-Feng
authors.initials: XF
authors.lastname: Bai
authors.affiliation: Mathematical Biosciences Institute, The Ohio State University, Columbus, Ohio, United States of America; Department of Mathematics, The Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Avner
authors.initials: A
authors.lastname: Friedman
mesh_terms: D000465:Algorithms; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D064094:Interleukin-27 / Q000378:metabolism*; D008954:Models, Biological; D008962:Models, Theoretical; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D013997:Time Factors
chemical_list: D016207:Cytokines; D064094:Interleukin-27