RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Long-term maintenance of patient-specific characteristics in tumoroids from six cancer indications.
Long-term maintenance of patient-specific characteristics in tumoroids from six cancer indications.
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肿瘤类器官,有时被称为癌症类器官,是患者来源的癌细胞以3D、自组织的多细胞结构形式生长,保持其来源肿瘤的关键特征(例如基因型、基因表达水平)。这些模型已成为研究肿瘤生物学、细胞毒性以及患者来源细胞对癌症治疗反应的有价值工具。
然而,肿瘤类器官的建立和维持历来具有挑战性、劳动强度大,且在不同实验室之间高度可变,阻碍了其广泛应用。在此,我们使用标准化的、无血清的Gibco OncoPro Tumoroid Culture Medium表征了结直肠、肺、头颈、乳腺、胰腺和子宫内膜肿瘤类器官的建立和/或扩增。新衍生的肿瘤类器官系(n = 20)通过靶向基因组分析和RNA测序进行分析,并且能够代表肿瘤组织样本。肿瘤类器官系在培养中稳定超过250天,并且能够冻融。先前建立的肿瘤类器官系也过渡到OncoPro培养基,与原始培养基系统相比,平均表现出相似的生长速率和保守的供体特异性特征。
此外,OncoPro培养基与细胞外基质包埋培养和悬浮培养形式均兼容,便于培养和放大。这些模型用于评估NK 细胞系和原代NK 细胞在不同时间点和不同剂量下的细胞毒性的一个示例应用,证明了这些模型与化合物和细胞治疗开发中使用的测定方法兼容。
我们预期该方法的标准化和通用性将对基础癌症研究、药物发现和个性化医疗产生重要益处,并有助于使肿瘤样模型更易于为癌症研究界所使用。
Tumoroids, sometimes referred to as cancer organoids, are patient-derived cancer cells grown as 3D, self-organized multicellular structures that maintain key characteristics (e. g. , genotype, gene expression levels) of the tumor from which they originated. These models have emerged as valuable tools for studying tumor biology, cytotoxicity, and response of patient-derived cells to cancer therapies.
However, the establishment and maintenance of tumoroids has historically been challenging, labor intensive, and highly variable from lab to lab, hindering their widespread use.
Here, we characterize the establishment and/or expansion of colorectal, lung, head and neck, breast, pancreas, and endometrial tumoroids using the standardized, serum-free Gibco OncoPro Tumoroid Culture Medium. Newly derived tumoroid lines (n = 20) were analyzed by targeted genomic profiling and RNA sequencing and were representative of tumor tissue samples.
Tumoroid lines were stable for over 250 days in culture and freeze-thaw competent. Previously established tumoroid lines were also transitioned to OncoPro medium and exhibited, on average, similar growth rates and conserved donor-specific characteristics when compared to original media systems.
Additionally, OncoPro medium was compatible with both embedded culture in extracellular matrix and growth in a suspension format for facile culture and scale up. An example application of these models for assessing the cytotoxicity of a natural killer cell line and primary natural killer cells over time and at various doses demonstrated the compatibility of these models with assays used in compound and cell therapy development.
We anticipate that the standardization and versatility of this approach will have important benefits for basic cancer research, drug discovery, and personalized medicine and help make tumoroid models more accessible to the cancer research community.
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