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

• Published in: PloS one 2014-03, Vol.9 (3), p.e91844
• Main Authors: Liao, Kang-Ling, Bai, Xue-Feng, Friedman, Avner
• Format: Article
• Language: English
• Subjects: Algorithms; Analysis; Anticancer properties; Antigens; Biocompatibility; Biological response modifiers; Biology and Life Sciences; Cancer; Cancer treatment; CD8 antigen; Chemical compounds; Computer and Information Sciences; Computer simulation; Cytokines; Cytokines - metabolism; Cytotoxicity; Gene expression; Health aspects; Humans; Immunology; Immunoregulation; Immunotherapy; Inflammation; Interferon; Interleukin 10; Interleukin 12; Interleukin 27; Interleukin-27 - metabolism; Interleukins; Lymphocytes; Lymphocytes T; Mathematical analysis; Mathematical models; Medicine and Health Sciences; Melanoma; Models, Biological; Models, Theoretical; Neoplasms - immunology; Neoplasms - metabolism; Partial differential equations; Pharmacology; Physical Sciences; Protocol (computers); Qualitative analysis; Rodents; Studies; T cells; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Time Factors; Tumor cells
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0091844

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.