Mathematical modeling of interleukin-27 induction of anti-tumor T cells response.
Mathematical modeling of interleukin-27 induction of anti-tumor T cells response.
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DOI：
10.1371/journal.pone.0091844
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Friedman A
中科院分区：
文献类型：
--
作者：
Liao KL;Bai XF;Friedman A
白细胞介素-12是一种促炎细胞因子，可促进Th1和细胞毒性T淋巴细胞的活性，如干扰素-的分泌。因此，白细胞介素-12可能是治疗癌症的一种强有力的药物。然而，白细胞介素-12也有剧毒。白细胞介素-27是一种来自白细胞介素-12家族的免疫调节细胞因子，但它的毒性不如白细胞介素-12。近年来，白细胞介素-27被认为是一种潜在的抗肿瘤药物。最近的体外和体内实验表明，转染IL-27的癌细胞激活CD8+ T细胞，促进抗肿瘤细胞因子白介素-10的分泌，尽管同时IL-27抑制CD8+ T细胞分泌干扰素-。本文根据这些实验结果建立了一个数学模型。该模型涉及一个包括肿瘤细胞、CD8+ T细胞和细胞因子白介素-27、白介素-10和干扰素-的动态网络。模拟模型显示了白细胞介素-27如何促进CD8+ T细胞分泌白细胞介素-10来抑制肿瘤生长。另一方面，白细胞介素-27抑制CD8+ T细胞分泌干扰素-，这在一定程度上减弱了对肿瘤生长的抑制作用。我们的数值结果与实验数据在定性上是一致的。我们利用该模型设计了IL-27注射治疗癌症的方案，发现对于某些特殊类型的癌症，在药物总量固定的情况下，在一定范围内，持续注射在治疗过程中降低肿瘤负荷的效果优于间歇注射，尽管肿瘤负荷的降低只是暂时的。
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.
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DOI：
10.1073/pnas.0904846106
发表时间：
2009-07-07
影响因子：
11.1
作者：
Day, Judy;Friedman, Avner;Schlesinger, Larry S.
通讯作者：
Schlesinger, Larry S.
影响因子：
20.3
作者：
Fujii, S;Shimizu, K;Lotze, MT
通讯作者：
Lotze, MT
影响因子：
4.3
作者：
BYRNE, HM;CHAPLAIN, MAJ
通讯作者：
CHAPLAIN, MAJ
影响因子：
11.2
作者：
Hisada, M;Kamiya, S;Yoshimoto, T
通讯作者：
Yoshimoto, T
影响因子：
1.5
作者：
Car, BD;Eng, VM;Anderson, TD
通讯作者：
Anderson, TD