Mathematical model of tumor immune microenvironment with application to the combined therapy targeting the PD-1/PD-L1 pathway and IL-10 cytokine antibody

被引:0
作者
Zhang, Zixin [1 ]
Liang, Xiyin [1 ]
Qin, Jianyong [2 ]
Lei, Jinzhi [1 ]
机构
[1] Tiangong Univ, Ctr Appl Math, Sch Math Sci, Tianjin 300387, Peoples R China
[2] Liwan Cent Hosp Guangzhou, Liwan Rd 35, Guangzhou 510170, Peoples R China
基金
中国国家自然科学基金;
关键词
Mathematical model; Tumor immunity; PD-1/PD-L1; Cytokines; Immunotherapy; BREAST-CANCER; TGF-BETA; PDL1; CELL; GROWTH;
D O I
10.1007/s12064-024-00428-1
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
The tumor microenvironment constitutes a complex system shaped by the intricate interactions among tumor cells, immune cells, and cytokines. Within this environment, the interplay between immune cells and cytokines is crucial in influencing tumor growth and progression. Despite advancements in clinical tumor immunotherapy, there remains a gap in comprehensive simulations of tumor immune responses, particularly regarding cytokine-driven processes. This study aims to address this gap by investigating the regulatory interactions among tumor cells, immune cells, and cytokines to simulate the complexities of tumor immunotherapy. We develop a comprehensive modeling and computational framework incorporating PD-1 inhibitors and interleukin-10 (IL-10) antibodies. Through detailed mathematical analysis, we elucidate the impact of changes in the immune microenvironment on tumor cells number. Our findings highlight the significant therapeutic effect of anti-PD-1 and IL-10 inhibitors, with increased drug dosage correlating with a reduction in tumor burden. Furthermore, combination therapy demonstrates a marked extension of survival with reduced dosages compared to monotherapy. Based on model simulations, we proposed prognostic predictions by assessing the microenvironmental status before treatment. The findings indicate a promising method for enhancing treatment effectiveness and offering potential advantages to patients receiving tumor immunotherapy.
引用
收藏
页码:19 / 43
页数:25
相关论文
共 40 条
[1]   Assessment of Tumor Mutational Burden and Outcomes in Patients With Diverse Advanced Cancers Treated With Immunotherapy [J].
Aggarwal, Charu ;
Ben-Shachar, Rotem ;
Gao, Yinjie ;
Hyun, Seung Won ;
Rivers, Zachary ;
Epstein, Carrie ;
Kaneva, Kristiyana ;
Sangli, Chithra ;
Nimeiri, Halla ;
Patel, Jyoti .
JAMA NETWORK OPEN, 2023, 6 (05)
[2]  
[Anonymous], 2014, Springer Proc. Math. Stat.
[3]   Mathematical Modeling Reveals That the Administration of EGF Can Promote the Elimination of Lymph Node Metastases by PD-1/PD-L1 Blockade [J].
Benchaib, Mohamed Amine ;
Bouchnita, Anass ;
Volpert, Vitaly ;
Makhoute, Abdelkader .
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY, 2019, 7 (MAY)
[4]   Oscillations in cyclical neutropenia:: new evidence based on mathematical modeling [J].
Bernard, S ;
Bélair, J ;
Mackey, MC .
JOURNAL OF THEORETICAL BIOLOGY, 2003, 223 (03) :283-298
[5]   PDL1 expression is a poor- prognosis factor in soft-tissue sarcomas [J].
Bertucci, Francois ;
Finetti, Pascal ;
Perrot, Delphine ;
Leroux, Agnes ;
Collin, Francoise ;
Le Cesned, Axel ;
Coindre, Jean-Michel ;
Blay, Jean-Yves ;
Birnbaum, Daniel ;
Mamessier, Emilie .
ONCOIMMUNOLOGY, 2017, 6 (03)
[6]   PDL1 expression is associated with longer postoperative, survival in adrenocortical carcinoma [J].
Billon, Emilien ;
Finetti, Pascal ;
Bertucci, Alexandre ;
Niccoli, Patricia ;
Birnbaum, Daniel ;
Mamessier, Emilie ;
Bertucci, Francois .
ONCOIMMUNOLOGY, 2019, 8 (11)
[7]   Mathematical prediction of clinical outcomes in advanced cancer patients treated with checkpoint inhibitor immunotherapy [J].
Butner, Joseph D. ;
Elganainy, Dalia ;
Wang, Charles X. ;
Wang, Zhihui ;
Chen, Shu-Hsia ;
Esnaola, Nestor F. ;
Pasqualini, Renata ;
Arap, Wadih ;
Hong, David S. ;
Welsh, James ;
Koay, Eugene J. ;
Cristini, Vittorio .
SCIENCE ADVANCES, 2020, 6 (18)
[8]   New PDL1 inhibitors for non-small cell lung cancer: focus on pembrolizumab [J].
Bylicki, Olivier ;
Paleiron, Nicolas ;
Rousseau-Bussac, Gaelle ;
Chouaid, Christos .
ONCOTARGETS AND THERAPY, 2018, 11 :4051-4064
[9]  
Filippova Natalia, 2018, J Cancer Sci Ther, V10, P190, DOI 10.4172/1948-5956.1000543
[10]  
Han YY, 2020, AM J CANCER RES, V10, P727