Mathematical modeling of Interleukin-27 induction of anti-tumor T cells response

doi:10.1371/journal.pone.0091844

機構典藏 > College of Sciences > Department of Applied Mathematics and Data Science > Journal Article > Item 987654321/111820

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Title:	Mathematical modeling of Interleukin-27 induction of anti-tumor T cells response
Authors:	Kang-Ling Liao, Xue-Feng Bai, and Avner Friedman
Date:	2014-03-14
Issue Date:	2017-10-25 02:10:46 (UTC+8)
Abstract:	Interleukin-12 is a pro-inflammatory cytokine which promotes Th1 and cytotoxic T lymphocyte activities, such as Interferon- 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- 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-. 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- 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.
Relation:	PLoS One. 2014 Mar 14;9(3):e91844.
DOI:	10.1371/journal.pone.0091844
Appears in Collections:	[Department of Applied Mathematics and Data Science] Journal Article

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