Combination therapy for cancer with IL-27 and anti-PD-1: A simplified mathematical model

IF 0.4 Q4 MATHEMATICS, APPLIED
Kenton D. Watt, Kang-Ling Liao
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引用次数: 0

Abstract

Many experiential and clinical trials in cancer treatment show that a combination of immune checkpoint inhibitor with another agent can improve the tumor reduction. Anti Programmed death 1 (Anti-PD-1) is one of these immune checkpoint inhibitors that re-activate immune cells to inhibit tumor growth.  In this work, we consider a combination treatment of anti-PD-1 and Interleukin-27 (IL-27). IL-27 has anti-cancer functions to promote the development of Th1 and CD8$^+$ T cells, but it also upregulates the expression of PD-1 and Programmed death ligand 1 (PD-L1) to inactivate these T cells. Thus, the functions of IL-27 in tumor growth is controversial. Hence, we create a simplified mathematical model to investigate whether IL-27 is pro-cancer or anti-cancer in the combination with anti-PD-1 and to what degree anti-PD-1 improves the efficacy of IL-27. Our synergy analysis for the combination treatment of IL-27 and anti-PD-1 shows that (i) ant-PD-1 can efficiently improve the treatment efficacy of IL-27; and (ii) there exists a monotone increasing function $F_c(G)$ depending on the treatment efficacy of anti-PD-1 $G$ such that IL-27 is an efficient anti-cancer agent when its dose is smaller than $F_c(G)$, whereas IL-27 is a pro-cancer agent when its dose is higher than $F_c(G)$. Our analysis also provides the existence and the local stability of the trivial, non-negative, and positive equilibria of the model. Combining with simulation, we discuss the effect of the IL-27 dosage on the equilibria and find that the T cells and IFN-$\gamma$ could vanish and tumor cells preserve, when the production rate of T cells by IL-27 is low or the dosage of IL-27 is low.
IL-27和抗pd -1联合治疗癌症:一个简化的数学模型
癌症治疗的许多经验和临床试验表明,免疫检查点抑制剂与另一种药物的组合可以改善肿瘤的减少。抗程序性死亡1(Anti-PD-1)是这些免疫检查点抑制剂之一,可重新激活免疫细胞以抑制肿瘤生长。在这项工作中,我们考虑了抗PD-1和白细胞介素-27(IL-27)的联合治疗。IL-27具有促进Th1和CD8$^+$T细胞发育的抗癌功能,但它也上调PD-1和程序性死亡配体1(PD-L1)的表达以灭活这些T细胞。因此,IL-27在肿瘤生长中的作用是有争议的。因此,我们创建了一个简化的数学模型来研究IL-27与抗PD-1的组合是抗癌还是抗癌,以及抗PD-1在多大程度上提高了IL-27的疗效。我们对IL-27和抗PD-1联合治疗的协同作用分析表明:(i)ant-PD-1可以有效提高IL-27的治疗效果;和(ii)存在单调递增函数$F_c(G)$,其取决于抗PD-1$G$的治疗效果,使得当其剂量小于$F_c)$时,IL-27是有效的抗癌剂,而当其剂量高于$F_c。我们的分析还提供了该模型平凡平衡、非负平衡和正平衡的存在性和局部稳定性。结合模拟,我们讨论了IL-27剂量对平衡的影响,发现当IL-27产生T细胞的速率较低或IL-27剂量较低时,T细胞和IFN-γ$可以消失,肿瘤细胞可以保留。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
1.40
自引率
0.00%
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0
审稿时长
21 weeks
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