← 返回

CAR-T 细胞治疗中的几何免疫抑制:数学建模的启示

英文原题:Geometric immunosuppression in CAR T-cell treatment: Insights from mathematical modeling.

查看英文原题

Geometric immunosuppression in CAR T-cell treatment: Insights from mathematical modeling.

PubMed 2025/06/11(内容时间) Comput Biol Med

分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。

中文摘要

CAR-T(CAR-T)细胞疗法已成为血液系统恶性肿瘤的一种有前景的治疗方法,为癌症治疗提供了一种靶向策略。由于肿瘤微环境内复杂的相互作用,理解CAR-T 细胞疗法在实体瘤中的复杂性面临挑战。数学建模可能作为一种有价值的工具,用以揭示CAR-T 细胞疗法的动态并提高其在实体瘤中的有效性。

本研究旨在利用元胞自动机进行建模,探讨空间因素在实体瘤CAR-T 治疗中的影响。我们的主要目标是通过分析不同空间分布以及改变肿瘤和CAR-T 细胞初始数量的情景,加深对治疗效果的理解。在计算机模拟中,肿瘤几何形状显著影响治疗效果,块状排列的肿瘤与稀疏细胞分布的肿瘤之间观察到显著差异,从而引出了由几何效应导致免疫抑制的概念。

本研究深入探讨了空间动态与实体瘤CAR-T 治疗有效性之间的复杂关系,强调了肿瘤几何形状在细胞免疫治疗结局中的相关性。我们的结果为提高CAR-T 细胞治疗疗效提供了基础,即通过将其与其他减少致密肿瘤区域密度的方法联合使用,从而为肿瘤杀伤T细胞打开通路。

展开英文摘要原文

Chimeric antigen receptor T (CAR T) cell therapy has emerged as a promising treatment for hematological malignancies, offering a targeted approach to cancer treatment. Understanding the complexities of CAR T-cell therapy within solid tumors poses challenges due to the intricate interactions within the tumor microenvironment. Mathematical modeling may serve as a valuable tool to unravel the dynamics of CAR T-cell therapy and improve its effectiveness in solid tumors.

This study aimed to investigate the impact of spatial aspects in CAR T therapy of solid tumors, utilizing cellular automata for modeling purposes.

Our main objective was to deepen our understanding of treatment effects by analyzing scenarios with different spatial distributions and varying the initial quantities of tumor and CAR T-cells. Tumor geometry significantly influenced treatment efficacy in-silico, with notable differences observed between tumors with block-like arrangements and those with sparse cell distributions, leading to the concept of immune suppression due to geometrical effects.

This research delves into the intricate relationship between spatial dynamics and the effectiveness of CAR T therapy in solid tumors, highlighting the relevance of tumor geometry in the outcome of cellular immunotherapy treatments.

Our results provide a basis for improving the efficacy of CAR T-cell treatments by combining them with other ones reducing the density of compact tumor areas and thus opening access ways for tumor killing T-cells.

论文信息

作者
Bordel-Vozmediano S、Sabir S、Benito-Barca L、Weigelin B、Pérez-García VM
单位
Mathematical Oncology Laboratory (MOLAB), Instituto de Matemática Aplicada a la Ciencia y la Ingeniería, Universidad de Castilla-La Mancha, Ciudad Real, 13005, Spain; Departamento de Matemáticas, Escuela Técnica Superior de Ingenieros Industriales, Universidad de Castilla-La Mancha, 13005, Ciudad Real, Spain. Electronic address: silvia.bordel@uclm.es.Spain
期刊
Computers in biology and medicine2025 Aug
原文标识
PubMed 40505286 · DOI 10.1016/j.compbiomed.2025.110427