工程化益生菌用于肿瘤靶向联合化学免疫治疗
Engineered probiotics for tumor-targeted combination chemoimmunotherapy.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
揭示工程化 T 细胞在患者癌症类器官中的作用机制
英文原题：Uncovering the mode of action of engineered T cells in patient cancer organoids.
查看英文原题
Uncovering the mode of action of engineered T cells in patient cancer organoids.
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中文摘要
将针对血癌的细胞免疫疗法成功扩展到实体瘤领域，需要改进的体外模型，以在分子水平揭示治疗作用模式。在此，我们描述了一个名为BEHAV3D的系统，该系统通过成像和转录组学开发用于研究免疫细胞与患者癌症类器官的动态相互作用。我们将BEHAV3D应用于实时追踪与患者来源的实体瘤类器官共培养的超过150,000个工程化T细胞，识别出一个包含具有强效连续杀伤能力的T细胞的“超级接合器”行为簇。在其他T细胞概念中，我们还研究了癌症代谢组感知工程化T细胞（TEGs），并检测到行为特异性基因特征，其中包括一组27个先前未描述T细胞功能的基因，这些基因由超级接合器杀伤性TEGs表达。我们进一步表明，I型干扰素可以预处理耐药类器官，使其对TEG介导的杀伤敏感。BEHAV3D是一种有前景的工具，用于表征细胞免疫疗法的行为-表型异质性，并可能支持个性化实体瘤靶向细胞疗法的优化。
展开英文摘要原文
Extending the success of cellular immunotherapies against blood cancers to the realm of solid tumors will require improved in vitro models that reveal therapeutic modes of action at the molecular level.
Here we describe a system, called BEHAV3D, developed to study the dynamic interactions of immune cells and patient cancer organoids by means of imaging and transcriptomics.
We apply BEHAV3D to live-track >150,000 engineered T cells cultured with patient-derived, solid-tumor organoids, identifying a 'super engager' behavioral cluster comprising T cells with potent serial killing capacity. Among other T cell concepts we also study cancer metabolome-sensing engineered T cells (TEGs) and detect behavior-specific gene signatures that include a group of 27 genes with no previously described T cell function that are expressed by super engager killer TEGs.
We further show that type I interferon can prime resistant organoids for TEG-mediated killing. BEHAV3D is a promising tool for the characterization of behavioral-phenotypic heterogeneity of cellular immunotherapies and may support the optimization of personalized solid-tumor-targeting cell therapies.
论文信息
- 作者
- Dekkers JF、Alieva M、Cleven A、Keramati F、Wezenaar AKL、van Vliet EJ、Puschhof J、Brazda P
- 第一作者单位
- Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center Utrecht, Utrecht, the Netherlands.Netherlands
- 通讯作者单位
- Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands. a.c.rios@prinsesmaximacentrum.nl.Netherlands
- 文献类型
- 非美国政府资助研究
- 期刊
- Nature biotechnology2023 Jan
- 原文标识
- PubMed 35879361 · DOI 10.1038/s41587-022-01397-w
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