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Patient-derived tumor-like cell clusters for personalized chemo- and immunotherapies in non-small cell lung cancer
Cell Stem Cell ( IF 19.8 ) Pub Date : 2024-04-08 , DOI: 10.1016/j.stem.2024.03.008
Shenyi Yin 1 , Ying Yu 1 , Nan Wu 2 , Minglei Zhuo 2 , Yanmin Wang 1 , Yanjie Niu 3 , Yiqian Ni 3 , Fang Hu 3 , Cuiming Ding 4 , Hongsheng Liu 5 , Xinghua Cheng 3 , Jin Peng 3 , Juan Li 1 , Yang He 1 , Jiaxin Li 1 , Junyi Wang 1 , Hanshuo Zhang 6 , Xiaoyu Zhai 2 , Bing Liu 2 , Yaqi Wang 2 , Shi Yan 2 , Mailin Chen 2 , Wenqing Li 2 , Jincui Peng 4 , Fei Peng 4 , Ruibin Xi 7 , Buqing Ye 1 , Liyan Jiang 3 , Jianzhong Jeff Xi 1
Affiliation  

Many patient-derived tumor models have emerged recently. However, their potential to guide personalized drug selection remains unclear. Here, we report patient-derived tumor-like cell clusters (PTCs) for non-small cell lung cancer (NSCLC), capable of conducting 100–5,000 drug tests within 10 days. We have established 283 PTC models with an 81% success rate. PTCs contain primary tumor epithelium self-assembled with endogenous stromal and immune cells and show a high degree of similarity to the original tumors in phenotypic and genotypic features. Utilizing standardized culture and drug-response assessment protocols, PTC drug-testing assays reveal 89% overall consistency in prospectively predicting clinical outcomes, with 98.1% accuracy distinguishing complete/partial response from progressive disease. Notably, PTCs enable accurate prediction of clinical outcomes for patients undergoing anti-PD1 therapy by combining cell viability and IFN-γ value assessments. These findings suggest that PTCs could serve as a valuable preclinical model for personalized medicine and basic research in NSCLC.



中文翻译:


用于非小细胞肺癌个性化化疗和免疫治疗的患者来源的肿瘤样细胞簇



最近出现了许多源自患者的肿瘤模型。然而,它们指导个性化药物选择的潜力仍不清楚。在这里,我们报告了来自患者的非小细胞肺癌 (NSCLC) 肿瘤样细胞簇 (PTC),能够在 10 天内进行 100-5,000 次药物测试。我们已经建立了 283 个 PTC 模型,成功率为 81%。 PTC包含由内源性基质细胞和免疫细胞自组装的原发肿瘤上皮,在表型和基因型特征上与原始肿瘤具有高度相似性。利用标准化培养和药物反应评估方案,PTC 药物测试分析显示,前瞻性预测临床结果的总体一致性为 89%,区分完全/部分反应与进展性疾病的准确度为 98.1%。值得注意的是,PTC 通过结合细胞活力和 IFN-γ 值评估,能够准确预测接受抗 PD1 治疗的患者的临床结果。这些发现表明 PTC 可以作为 NSCLC 个性化医疗和基础研究的有价值的临床前模型。

更新日期:2024-04-08
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