Mathematical modeling of interleukin-27 induction of anti-tumor T cells response.
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. Inte...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3954918?pdf=render |
| _version_ | 1811331134206771200 |
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| author | Kang-Ling Liao Xue-Feng Bai Avner Friedman |
| author_facet | Kang-Ling Liao Xue-Feng Bai Avner Friedman |
| author_sort | Kang-Ling Liao |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T16:14:35Z |
| format | Article |
| id | doaj.art-119dc465a8bb409694f1d9f63bc2eb42 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T16:14:35Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-119dc465a8bb409694f1d9f63bc2eb422022-12-22T02:40:05ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0193e9184410.1371/journal.pone.0091844Mathematical modeling of interleukin-27 induction of anti-tumor T cells response.Kang-Ling LiaoXue-Feng BaiAvner FriedmanInterleukin-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.http://europepmc.org/articles/PMC3954918?pdf=render |
| spellingShingle | Kang-Ling Liao Xue-Feng Bai Avner Friedman Mathematical modeling of interleukin-27 induction of anti-tumor T cells response. PLoS ONE |
| title | Mathematical modeling of interleukin-27 induction of anti-tumor T cells response. |
| title_full | Mathematical modeling of interleukin-27 induction of anti-tumor T cells response. |
| title_fullStr | Mathematical modeling of interleukin-27 induction of anti-tumor T cells response. |
| title_full_unstemmed | Mathematical modeling of interleukin-27 induction of anti-tumor T cells response. |
| title_short | Mathematical modeling of interleukin-27 induction of anti-tumor T cells response. |
| title_sort | mathematical modeling of interleukin 27 induction of anti tumor t cells response |
| url | http://europepmc.org/articles/PMC3954918?pdf=render |
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