دورية أكاديمية
Mathematical modeling and analysis of cancer treatment with radiation and anti-PD-L1.
العنوان: | Mathematical modeling and analysis of cancer treatment with radiation and anti-PD-L1. |
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المؤلفون: | Liao KL; Department of Mathematics, University of Manitoba, Winnipeg, Manitoba, R3T 2N2, Canada. Electronic address: Kang-Ling.Liao@umanitoba.ca., Wieler AJ; Department of Mathematics, University of Manitoba, Winnipeg, Manitoba, R3T 2N2, Canada., Gascon PML; Department of Mathematics, University of Manitoba, Winnipeg, Manitoba, R3T 2N2, Canada. |
المصدر: | Mathematical biosciences [Math Biosci] 2024 Aug; Vol. 374, pp. 109218. Date of Electronic Publication: 2024 May 24. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: American Elsevier Country of Publication: United States NLM ID: 0103146 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-3134 (Electronic) Linking ISSN: 00255564 NLM ISO Abbreviation: Math Biosci Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: New York, American Elsevier. |
مواضيع طبية MeSH: | Neoplasms*/immunology , Neoplasms*/radiotherapy , Neoplasms*/drug therapy, Humans ; B7-H1 Antigen/antagonists & inhibitors ; Immune Checkpoint Inhibitors/therapeutic use ; Immune Checkpoint Inhibitors/pharmacology ; Mathematical Concepts ; Models, Theoretical |
مستخلص: | In cancer treatment, radiation therapy (RT) induces direct tumor cell death due to DNA damage, but it also enhances the deaths of radiosensitive immune cells and is followed by local relapse and up-regulation of immune checkpoint ligand PD-L1. Since the binding between PD-1 and PD-L1 curtails anti-tumor immunities, combining RT and PD-L1 inhibitor, anti-PD-L1, is a potential method to improve the treatment efficacy by RT. Some experiments support this hypothesis by showing that the combination of ionizing irradiation (IR) and anti-PD-L1 improves tumor reduction comparing to the monotherapy of IR or anti-PD-L1. In this work, we create a simplified ODE model to study the order of tumor growths under treatments of IR and anti-PD-L1. Our synergy analysis indicates that both IR and anti-PD-L1 improve the tumor reduction of each other, when IR and anti-PD-L1 are given simultaneously. When giving IR and anti-PD-L1 separately, a high dosage of IR should be given first to efficiently reduce tumor load and then followed by anti-PD-L1 with strong efficacy to maintain the tumor reduction and slow down the relapse. Increasing the duration of anti-PD-L1 improves the tumor reduction, but it cannot prolong the duration that tumor relapses to the level of the control case. Under some simplification, we also prove that the model has an unstable tumor free equilibrium and a locally asymptotically stable tumor persistent equilibrium. Our bifurcation diagram reveals a transition from tumor elimination to tumor persistence, as the tumor growth rate increases. In the tumor persistent case, both anti-PD-L1 and IR can reduce tumor amount in the long term. Competing Interests: Declaration of competing interest There is no conflict of interest. (Copyright © 2024 Elsevier Inc. All rights reserved.) |
فهرسة مساهمة: | Keywords: Anti-PD-L1; Immune checkpoint inhibitor; ODE model; Radiation therapy; Tumor relapse |
المشرفين على المادة: | 0 (B7-H1 Antigen) 0 (Immune Checkpoint Inhibitors) 0 (CD274 protein, human) |
تواريخ الأحداث: | Date Created: 20240526 Date Completed: 20240714 Latest Revision: 20240812 |
رمز التحديث: | 20240813 |
DOI: | 10.1016/j.mbs.2024.109218 |
PMID: | 38797473 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1879-3134 |
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DOI: | 10.1016/j.mbs.2024.109218 |