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用于研究免疫细胞浸润与细胞毒性联合作用的 3D 多隔室组装体

英文原题：A 3D multi-compartment assembloid to study combined immune cell infiltration and cytotoxicity.

查看英文原题

A 3D multi-compartment assembloid to study combined immune cell infiltration and cytotoxicity.

PubMed 2026/02/13（内容时间） Cell Rep Methods Q1 · IF 5.8（JCR 2025）

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实体瘤地区：美国
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中文摘要

实体瘤中免疫细胞杀伤癌细胞之前，必须经历多步骤浸润级联过程，包括侵入、定向迁移及细胞毒作用。标准体外细胞毒实验在无障碍二维（2D）微环境中测量免疫细胞杀伤，因此无法研究三维环境下免疫细胞与细胞外基质（ECM）的相互作用。本研究采用三维多区室组装体模型，综合研究免疫细胞侵入基质并在其中迁移、随后侵入实体瘤并最终发挥细胞毒作用的全过程。研究使用未经改造的免疫细胞和嵌合抗原受体（CAR）T细胞，将该三维细胞毒实验与基准二维细胞毒实验进行比较。该实验可结合多种成像技术，直接观察并定量不同免疫和肿瘤背景下浸润的各个阶段。研究凸显三维浸润/细胞毒实验作为机制研究工具的重要价值，可用于研究免疫细胞与肿瘤微环境的相互作用。

展开英文摘要原文

Immune cell-mediated killing of cancer cells in a solid tumor is prefaced by a multi-step infiltration cascade of invasion, directed migration, and cytotoxic activities. Standard in vitro cytotoxicity assays measure immune cell killing in obstacle-free, two-dimensional (2D) microenvironments, which preclude the study of 3D immune cell-extracellular matrix (ECM) interactions.

Here, we use a 3D multi-compartment assembloid for the combined study of immune cell stromal invasion and matrix migration, followed by invasion of the solid tumor and subsequent cytotoxicity.

We compare this 3D cytotoxicity assay to the benchmark 2D cytotoxicity assay using both unmodified immune cells and chimeric antigen receptor (CAR) T cells. This assay is amenable to a range of imaging techniques, allowing for the direct observation and quantification of each stage of infiltration in various immune and oncological contexts.

We highlight the value of the 3D infiltration/cytotoxicity assay as an important tool for the mechanistic study of immune cell interactions with the tumor microenvironment.

论文信息

作者
Hanna EA、Crawford AJ、Du W、Johnston A、Schell D、Wan Z、Chen TH、Wu F
第一作者单位
Johns Hopkins Institute for Nanobiotechnology, Johns Hopkins Physical Sciences-Oncology Center, The Johns Hopkins University, Baltimore, MD 21218, USA; Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, MD 21218, USA.United States
通讯作者单位
Johns Hopkins Institute for Nanobiotechnology, Johns Hopkins Physical Sciences-Oncology Center, The Johns Hopkins University, Baltimore, MD 21218, USA; Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, MD 21218, USA; Department of Biomedical Engineering, The Johns Hopkins University, Baltimore, MD 21218, USA; Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA. Electronic address: wirtz@jhu.edu.United States
期刊
Cell reports methods2026 Feb 23
原文标识
PubMed 41690308　·　DOI 10.1016/j.crmeth.2026.101307

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