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
患者来源的微器官球可实现临床精准肿瘤学
英文原题：Patient-derived micro-organospheres enable clinical precision oncology.
查看英文原题
Patient-derived micro-organospheres enable clinical precision oncology.
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中文摘要
患者来源异种移植（PDX）和患者来源类器官（PDO）已被证明可模拟癌症治疗的临床反应。然而，利用这些模型指导癌症患者的及时临床决策仍具挑战性。在此，我们采用带温度控制和死体积最小化的液滴乳剂微流控技术，从低体积患者组织中快速生成数千个微器官球（MOS），其可作为临床精准肿瘤学的理想患者来源模型。一项针对新诊断转移性结直肠癌（CRC）患者的临床研究使用基于 MOS 的精准肿瘤学流程，在 14 天内可靠评估了肿瘤药物反应，这一时间线适合指导临床治疗决策。此外，MOS 可捕获原始基质细胞并允许 T 细胞穿透，为在患者肿瘤上测试免疫肿瘤（IO）疗法（如 PD-1 阻断、双特异性抗体和 T 细胞疗法）提供了临床检测方法。
展开英文摘要原文
Patient-derived xenografts (PDXs) and patient-derived organoids (PDOs) have been shown to model clinical response to cancer therapy.
However, it remains challenging to use these models to guide timely clinical decisions for cancer patients.
Here, we used droplet emulsion microfluidics with temperature control and dead-volume minimization to rapidly generate thousands of micro-organospheres (MOSs) from low-volume patient tissues, which serve as an ideal patient-derived model for clinical precision oncology. A clinical study of recently diagnosed metastatic colorectal cancer (CRC) patients using an MOS-based precision oncology pipeline reliably assessed tumor drug response within 14 days, a timeline suitable for guiding treatment decisions in the clinic.
Furthermore, MOSs capture original stromal cells and allow T cell penetration, providing a clinical assay for testing immuno-oncology (IO) therapies such as PD-1 blockade, bispecific antibodies, and T cell therapies on patient tumors.
论文信息
- 作者
- Ding S、Hsu C、Wang Z、Natesh NR、Millen R、Negrete M、Giroux N、Rivera GO
- 第一作者单位
- Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC 27708, USA; Xilis, Inc., Durham, NC 27713, USA.United States
- 通讯作者单位
- Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC 27708, USA; Terasaki Institute for Biomedical Innovation, Los Angeles, CA 90024, USA. Electronic address: xiling.shen@terasaki.org.United States
- 文献类型
- 美国 NIH 资助研究 · 非美国政府资助研究
- 期刊
- Cell stem cell2022 Jun 2
- 原文标识
- PubMed 35508177 · DOI 10.1016/j.stem.2022.04.006
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