A tumor-immune interaction model for hepatocellular carcinoma based on measured lymphocyte counts in patients undergoing radiotherapy.
A tumor-immune interaction model for hepatocellular carcinoma based on measured lymphocyte counts in patients undergoing radiotherapy.
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DOI：
10.1016/j.radonc.2020.07.025
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发表时间：
2020-10
期刊：
影响因子：
--
通讯作者：
Paganetti H
中科院分区：
文献类型：
--
作者：
Sung W;Grassberger C;McNamara AL;Basler L;Ehrbar S;Tanadini-Lang S;Hong TS;Paganetti H
放射治疗对免疫系统的影响最近引起了人们的关注，特别是当与免疫治疗联合使用时。然而，目前还不清楚不同的治疗分割方案如何影响免疫系统和辐射之间的相互作用。这项工作的目标是开发一个数学模型，量化的免疫刺激以及免疫抑制作用的放射治疗，并模拟不同的分割方案的影响，根据患者的数据。该框架描述了肿瘤细胞，淋巴细胞和灭活的垂死肿瘤细胞在放射治疗过程中释放抗原的时间演变，特别是模拟招募的淋巴细胞如何抑制肿瘤进展。模型的参数部分来自文献，部分来自接受放疗的肝细胞癌患者及其结局的血液样本（循环淋巴细胞：CL）。用概率模型计算循环淋巴细胞的剂量体积直方图。基于拟合的参数，该模型能够研究患者中CL的消耗和恢复作为分次方案的函数。我们的研究结果量化的能力，短的分割方案，导致淋巴细胞耗竭的时间更短，并预测治疗结束后更快的恢复。该模型表明，治疗之间的馏分可以延长淋巴细胞耗竭的时间，应该避免。本研究介绍了一个数学模型的肿瘤免疫相互作用，使用临床提取的放射治疗患者的数据，它可以应用于设计试验，旨在尽量减少淋巴细胞耗竭效应的放射治疗。
The impact of radiation therapy on the immune system has recently gained attention particularly when delivered in combination with immunotherapy. However, it is unclear how different treatment fractionation regimens influence the interaction between the immune system and radiation. The goal of this work was to develop a mathematical model that quantifies both the immune stimulating as well as the immunosuppressive effects of radiotherapy and simulates the effects of different fractionation regimens based on patient data. The framework describes the temporal evolution of tumor cells, lymphocytes, and inactivated dying tumor cells releasing antigens during radiation therapy, specifically modeling how recruited lymphocytes inhibit tumor progression. The parameters of the model were partly taken from the literature and in part extracted from blood samples (circulating lymphocytes: CLs) collected from hepatocellular carcinoma patients undergoing radiotherapy and their outcomes. The dose volume histograms to circulating lymphocytes were calculated with a probability-based model. Based on the fitted parameters, the model enabled a study into the depletion and recovery of CLs in patients as a function of fractionation regimen. Our results quantify the ability of short fractionation regimens to lead to shorter periods of lymphocyte depletion and predict faster recovery after the end of treatment. The model shows that treatment breaks between fractions can prolong the period of lymphocyte depletion and should be avoided. This study introduces a mathematical model for tumor-immune interactions using clinically extracted radiotherapy patient data, which can be applied to design trials aimed at minimizing lymphocyte depleting effects in radiation therapy.
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DOI：
10.1158/1541-7786.mcr-12-0492
发表时间：
2013-01
期刊：
Molecular cancer research : MCR
影响因子：
--
作者：
Makinde AY;John-Aryankalayil M;Palayoor ST;Cerna D;Coleman CN
通讯作者：
Coleman CN
影响因子：
3.5
作者：
Hammi A;Paganetti H;Grassberger C
通讯作者：
Grassberger C
DOI：
10.1158/1078-0432.ccr-09-0265
发表时间：
2009-09-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Dewan MZ;Galloway AE;Kawashima N;Dewyngaert JK;Babb JS;Formenti SC;Demaria S
通讯作者：
Demaria S
影响因子：
82.9
作者：
Long, Quan-Xin;Liu, Bai-Zhong;Huang, Ai-Long
通讯作者：
Huang, Ai-Long
影响因子：
2.2
作者：
Eftimie, R.;Macnamara, C. K.;Earn, D. J. D.
通讯作者：
Earn, D. J. D.