标题： CAR-T细胞治疗中的几何免疫抑制：数学建模的见解 显示英文标题

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

摘要： 嵌合抗原受体T（CAR-T）细胞疗法已成为一种有前景的血液系统恶性肿瘤治疗方法，提供了针对癌症治疗的靶向方法。 由于肿瘤微环境内的复杂相互作用，理解CAR-T细胞疗法在实体瘤中的复杂性存在挑战。 数学建模可能成为一种有价值的工具，以解析CAR-T细胞疗法的动力学并提高其在实体瘤中的效果。 本研究旨在探讨实体瘤CAR-T治疗中空间因素的影响，利用细胞自动机进行建模。 我们的主要目标是通过分析不同空间分布的情况以及改变肿瘤细胞和CAR-T细胞的初始数量，加深对治疗效果的理解。 肿瘤几何形状显著影响了计算机模拟中的治疗效果，块状排列的肿瘤与稀疏细胞分布的肿瘤之间观察到了显著差异，导致了由于几何效应引起的免疫抑制概念。 这项研究深入探讨了空间动力学与实体瘤中CAR-T疗法效果之间的复杂关系，强调了肿瘤几何形状在细胞免疫治疗结果中的相关性。 我们的结果为通过将CAR-T细胞治疗与其他方法结合，减少致密肿瘤区域的密度，从而为杀伤肿瘤的T细胞打开通路，提高CAR-T细胞治疗效果提供了基础。 显示英文摘要

摘要： 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.