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揭示黑色素瘤患者来源类器官模型中的治疗机会

英文原题:Unveiling Therapeutic Opportunities with Melanoma Patient-derived Organoid Models.

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Unveiling Therapeutic Opportunities with Melanoma Patient-derived Organoid Models.

PubMed 2024/09/06(内容时间) J Vis Exp Q3 · IF 1.2(JCR 2025)

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中文摘要

随着免疫治疗的发展,持续需要开发能够再现原发肿瘤微环境的模型。虽然传统的二维和三维模型可以提供对癌症发生和进展的见解,但这些模型缺乏一些关键方面,阻碍了对原发肿瘤的忠实模拟。一种备受关注的替代模型是患者来源的类器官。这些类器官的开发再现了复杂的细胞间通讯、肿瘤微环境和肿瘤的组织结构。本文描述了建立黑色素瘤患者来源类器官(MPDO)模型的方案。为了验证这些模型,我们评估了免疫细胞组成,包括T细胞活化标志物的表达水平,以确认类器官的细胞异质性。此外,为了描述MPDO在细胞治疗中的潜在用途,我们评估了用γδ T细胞处理类器官的细胞毒性能力。总之,MPDO模型为理解肿瘤复杂性、验证治疗策略以及可能推进个性化治疗提供了有前景的途径。

展开英文摘要原文

With the development of immunotherapy, there is an ongoing need to develop models that can recapitulate the tumor microenvironment of native tumors. While traditional two- and three-dimensional models can offer insights into cancer development and progression, these lack crucial aspects that hinder a faithful mimic of native tumors. An alternative model that has gained a lot of attention is the patient-derived organoid.

The development of these organoids recapitulates the complex intercellular communication, tumor microenvironment, and histoarchitecture of tumors. This paper describes the protocol for establishing melanoma patient-derived organoid (MPDO) models. To validate these models, we assessed the immune cell composition, including the expression levels of T-cell activation markers, to confirm the cellular heterogeneity of the organoids.

Additionally, to describe the potential utility of MPDOs in cellular therapies, we evaluated the cytotoxic capabilities of treating the organoids with γδ T-cells.

In conclusion, the MPDO models offer promising avenues for understanding tumor complexity, validating therapeutic strategies, and potentially advancing personalized treatment.

论文信息

作者
Goncalves B、Liu S、Zhang X、Fan A、Ou L、Xu X
第一作者单位
Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania.United States
通讯作者单位
Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania; xug@pennmedicine.upenn.edu.United States
文献类型
音视频资料 · 美国 NIH 资助研究
期刊
Journal of visualized experiments : JoVE2024 Sep 6
原文标识
PubMed 39311587 · DOI 10.3791/66509