Three-Dimensional Culture Models to Study Innate Anti-Tumor Immune Response: Advantages and Disadvantages.
Three-Dimensional Culture Models to Study Innate Anti-Tumor Immune Response: Advantages and Disadvantages.
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用于研究先天性抗肿瘤免疫反应的三维培养模型：优缺点
DOI：
10.3390/cancers13143417
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发表时间：
2021-07-08
期刊：
影响因子：
5.2
通讯作者：
Benelli R
中科院分区：
文献类型：
--
作者：
Poggi A;Villa F;Fernadez JLC;Costa D;Zocchi MR;Benelli R
研究针对肿瘤的免疫应答的经典方法是在几个实验环境中将免疫细胞与肿瘤细胞悬浮液混合。这些模型缺乏发生免疫应答的适当组织结构，并且没有考虑对于理解抗肿瘤免疫应答至关重要的肿瘤微环境的其他细胞和细胞外参与者。因此，为了确认体外数据，已经广泛地进行了体内实验，使用可能无法完全再现人类中发生的情况的动物模型。事实上，在基于动物的研究中，肿瘤是在短时间内人工产生的，并且参与免疫系统识别肿瘤细胞的免疫细胞亚群和受体-配体对通常与人类对应物不同。为了减少使用的动物数量，并可能取代动物模型，已经开发了替代的培养方法。在此，将描述这些方法中的一些，突出它们的优点和缺点，重点放在自然杀伤细胞作为能够对比肿瘤生长的第一线抗肿瘤效应细胞。几种方法已经表明，针对肿瘤的免疫应答强烈影响患者的临床结果。因此，抗肿瘤免疫的研究对于理解和加强消除肿瘤细胞的机制至关重要。自然杀伤（NK）细胞是先天免疫的成员，代表强大的抗肿瘤效应，能够消除肿瘤细胞，而无需预先致敏。因此，研究它们参与抗肿瘤反应对于临床翻译至关重要。该分析已在体外进行，将NK与肿瘤细胞共孵育并定量NK细胞的细胞毒性活性。体内确认已被应用于克服体外测试的限制，然而，小鼠和人的先天免疫力不同，导致差异。NK细胞上的不同活化受体和肿瘤细胞上的反配体参与抗肿瘤应答，并且先天免疫严格依赖于其发生的特定微环境。因此，已经创建了三维（3D）培养系统，其中NK细胞和肿瘤细胞可以在组织样结构中相互作用。例如，肿瘤细胞球状体和来源于几种肿瘤类型的原代类器官迄今已被用于分析先天免疫应答，取代动物模型。在此，我们简要介绍了NK细胞，并详细分析和讨论了三维肿瘤培养系统的特性及其用于研究肿瘤细胞与NK细胞的相互作用。
The classical approach to study the immune response against a tumor was mixing immune cells with tumor cell suspensions in several experimental settings. These models lack the appropriate tissue architecture in which the immune response takes place and do not consider other cellular and extracellular players of the tumor microenvironment essential to understand the anti-tumor immune response. Thus, to confirm in vitro data, in vivo experiments have been extensively performed, using animal models that may not fully reproduce what happens in humans. Indeed, in animal-based studies, tumors are artificially generated in a short time, and immune cell subsets and receptor-ligands pairs, involved in tumor cells recognition by the immune system, are often different from human counterparts. To reduce the number of animals used, and possibly replace animal models, alternative methods of culture have been developed. Herein, some of these approaches will be described, highlighting their advantages and disadvantages, focusing on natural killer cells as the first line of anti-tumor effector cells able to contrast tumor growth. Several approaches have shown that the immune response against tumors strongly affects patients’ clinical outcome. Thus, the study of anti-tumor immunity is critical to understand and potentiate the mechanisms underlying the elimination of tumor cells. Natural killer (NK) cells are members of innate immunity and represent powerful anti-tumor effectors, able to eliminate tumor cells without a previous sensitization. Thus, the study of their involvement in anti-tumor responses is critical for clinical translation. This analysis has been performed in vitro, co-incubating NK with tumor cells and quantifying the cytotoxic activity of NK cells. In vivo confirmation has been applied to overcome the limits of in vitro testing, however, the innate immunity of mice and humans is different, leading to discrepancies. Different activating receptors on NK cells and counter-ligands on tumor cells are involved in the antitumor response, and innate immunity is strictly dependent on the specific microenvironment where it takes place. Thus, three-dimensional (3D) culture systems, where NK and tumor cells can interact in a tissue-like architecture, have been created. For example, tumor cell spheroids and primary organoids derived from several tumor types, have been used so far to analyze innate immune response, replacing animal models. Herein, we briefly introduce NK cells and analyze and discuss in detail the properties of 3D tumor culture systems and their use for the study of tumor cell interactions with NK cells.
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影响因子：
7.3
作者：
Bödder J;Zahan T;van Slooten R;Schreibelt G;de Vries IJM;Flórez-Grau G
通讯作者：
Flórez-Grau G
在选择性缺乏CD3 Delta基因表达的CD3/TCR-人胸腺细胞种群的体外扩张：一种表型和功能分析。
影响因子：
15.3
作者：
Poggi, A;Biassoni, R;Pella, N;Paolieri, F;Bellomo, R;Bertolini, A;Moretta, L;Mingari, M C
通讯作者：
Mingari, M C
DOI：
10.1038/s41571-020-00455-z
发表时间：
2021-04
期刊：
Nature reviews. Clinical oncology
影响因子：
--
作者：
Braun DA;Bakouny Z;Hirsch L;Flippot R;Van Allen EM;Wu CJ;Choueiri TK
通讯作者：
Choueiri TK
影响因子：
5.2
作者：
Batista IA;Quintas ST;Melo SA
通讯作者：
Melo SA
DOI：
10.1084/jem.177.4.1117
发表时间：
1993-04-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Bellone G;Valiante NM;Viale O;Ciccone E;Moretta L;Trinchieri G
通讯作者：
Trinchieri G