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T 细胞疗法治疗癌症:基于临床前研究的预测弥散界面数学模型。

T cell therapy against cancer: A predictive diffuse-interface mathematical model informed by pre-clinical studies.

机构信息

MOX Laboratory, Department of Mathematics, Politecnico di Milano, Piazza Leonardo da Vinci 32, 20133 Milano, Italy.

Experimental Neurology (INSPE) and Experimental Imaging Center (CIS), Neuroscience Division, IRCCS Ospedale San Raffaele, Via Olgettina 60, 20132 Milan, Italy.

出版信息

J Theor Biol. 2022 Aug 21;547:111172. doi: 10.1016/j.jtbi.2022.111172. Epub 2022 May 26.

Abstract

T cell therapy has become a new therapeutic opportunity against solid cancers. Predicting T cell behaviour and efficacy would help therapy optimization and clinical implementation. In this work, we model responsiveness of mouse prostate adenocarcinoma to T cell-based therapies. The mathematical model is based on a Cahn-Hilliard diffuse interface description of the tumour, coupled with Keller-Segel type equations describing immune components dynamics. The model is fed by pre-clinical magnetic resonance imaging data describing anatomical features of prostate adenocarcinoma developed in the context of the Transgenic Adenocarcinoma of the Mouse Prostate model. We perform computational simulations based on the finite element method to describe tumor growth dynamics in relation to local T cells concentrations. We report that when we include in the model the possibility to activate tumor-associated vessels and by that increase the number of T cells within the tumor mass, the model predicts higher therapeutic effects (tumor regression) shortly after therapy administration. The simulated results are found in agreement with reported experimental data. Thus, this diffuse-interface mathematical model well predicts T cell behavior in vivo and represents a proof-of-concept for the role such predictive strategies may play in optimization of immunotherapy against cancer.

摘要

T 细胞疗法已成为针对实体瘤的一种新的治疗机会。预测 T 细胞的行为和疗效将有助于优化治疗和临床实施。在这项工作中,我们对小鼠前列腺腺癌对基于 T 细胞的治疗的反应进行建模。该数学模型基于肿瘤的 Cahn-Hilliard 扩散界面描述,以及描述免疫成分动力学的 Keller-Segel 型方程。该模型由描述在 Transgenic Adenocarcinoma of the Mouse Prostate 模型背景下发展的前列腺腺癌的解剖特征的临床前磁共振成像数据提供。我们基于有限元方法进行计算模拟,以描述与局部 T 细胞浓度相关的肿瘤生长动力学。我们报告说,当我们在模型中包含激活肿瘤相关血管的可能性,并由此增加肿瘤内的 T 细胞数量时,模型预测在治疗后不久会产生更高的治疗效果(肿瘤消退)。模拟结果与报告的实验数据一致。因此,这种弥散界面数学模型很好地预测了体内 T 细胞的行为,并为这种预测策略在癌症免疫治疗的优化中可能发挥的作用提供了概念验证。

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