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3D 肿瘤模型及其在免疫疗法测试中的应用。

3D Tumor Models and Their Use for the Testing of Immunotherapies.

机构信息

Cancer Research Center in Marseille, CRCM, Paoli Calmette Institute, Marseille, France.

出版信息

Front Immunol. 2020 Dec 10;11:603640. doi: 10.3389/fimmu.2020.603640. eCollection 2020.


DOI:10.3389/fimmu.2020.603640
PMID:33362787
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7758240/
Abstract

Over the past decade, immunotherapy has become a powerful and evident tool in the fight against cancers. Notably, the rise of checkpoint blockade using monoclonal antibodies (anti-CTLA4, anti-PD1) to avoid interaction between inhibitory molecules allowed the betterment of patient care. Indeed, immunotherapies led to increased overall survival in forms of cutaneous melanoma or lung cancer. However, the percentage of patients responding varies from 20 to 40% depending on the type of cancer and on the expression of the target molecules by the tumor. This is due to the tumor microenvironment which allows the acquisition of resistance mechanisms to immunotherapies by tumor cells. These are closely linked to the architecture and cellular composition of the tumor microenvironment. This one acts on different parameters such as the immune cells infiltrate its composition and therefore, favors the recruitment of immunosuppressive cells as well as the tumor expression of checkpoint inhibitors such as Programmed Death Ligand-1 (PD-L1). Therefore, the analysis and modeling of the complexity of the microenvironment is an important parameter to consider, not only in the search for new therapies but also for the identification and stratification of patients likely to respond to immunotherapy. This is why the use of 3D culture models, reflecting the architecture and cellular composition of a tumor, is essential in immuno-oncology studies. Nowadays, there are several 3-D culture methods such as spheroids and organoids, which are applicable to immuno-oncology. In this review we evaluate 3D culture models as tools for the development of treatments in the field of immuno-oncology.

摘要

在过去的十年中,免疫疗法已成为对抗癌症的一种强大而有效的手段。值得注意的是,使用单克隆抗体(抗 CTLA4、抗 PD1)阻断检查点以避免抑制分子相互作用的方法的出现,改善了患者的治疗效果。事实上,免疫疗法导致皮肤黑色素瘤或肺癌患者的总生存率提高。然而,根据癌症的类型和肿瘤靶分子的表达,应答患者的比例从 20%到 40%不等。这是由于肿瘤微环境使肿瘤细胞能够获得对免疫疗法的耐药机制。这些与肿瘤微环境的结构和细胞组成密切相关。肿瘤微环境通过不同的参数发挥作用,例如免疫细胞浸润其组成,因此有利于招募免疫抑制细胞以及肿瘤表达检查点抑制剂,如程序性死亡配体-1(PD-L1)。因此,分析和建模微环境的复杂性是一个重要的考虑因素,不仅在寻找新的治疗方法方面,而且在识别和分层可能对免疫疗法有反应的患者方面也是如此。这就是为什么使用 3D 培养模型来反映肿瘤的结构和细胞组成在免疫肿瘤学研究中至关重要的原因。如今,有几种 3D 培养方法,如球体和类器官,适用于免疫肿瘤学。在这篇综述中,我们评估了 3D 培养模型作为免疫肿瘤学领域治疗方法发展的工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed1a/7758240/9d980ad8e287/fimmu-11-603640-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed1a/7758240/9d980ad8e287/fimmu-11-603640-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed1a/7758240/9d980ad8e287/fimmu-11-603640-g001.jpg

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