免疫检查点阻断通过扩增效应 CD8⁺ T 细胞克隆增强淋巴细胞清除性化疗诱导的抗肿瘤免疫
Immune Checkpoint Blockade Augments Lymphodepleting Chemotherapy-Induced Antitumor Immunity by Expanding Effector CD8+ T-cell Clones.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
通过类肿瘤血管微流控装置进行黏附分析，鉴定出具有增强肿瘤归巢能力的 CD8(+) T 细胞以改善细胞治疗
英文原题：Adhesion analysis via a tumor vasculature-like microfluidic device identifies CD8(+) T cells with enhanced tumor homing to improve cell therapy.
查看英文原题
Adhesion analysis via a tumor vasculature-like microfluidic device identifies CD8(+) T cells with enhanced tumor homing to improve cell therapy.
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中文摘要
CD8+ T细胞向肿瘤微环境的募集对于过继细胞治疗（ACT）的成功至关重要。遗憾的是，只有一小部分转移的细胞能够归巢至实体瘤。黏附配体-受体相互作用已被认为参与CD8+ T细胞的归巢；然而，在血流动力学流动的影响下，CD8+ T细胞如何与肿瘤血管表达的黏附配体相互作用，目前尚缺乏了解。在此，利用一种工程化微流控装置在体外模拟CD8+ T细胞归巢至黑色素瘤的能力，该装置重现了肿瘤血管的血流动力学微环境。在体外流动条件下黏附增强、在体内肿瘤归巢增强的过继转移CD8+ T细胞，与免疫检查点阻断联合使用时，可改善ACT的肿瘤控制效果。这些结果表明，工程化微流控装置能够模拟肿瘤血管微环境，以鉴定具有增强肿瘤浸润能力的T细胞亚群，而这是ACT的一个关键限制因素。
展开英文摘要原文
CD8 + T cell recruitment to the tumor microenvironment is critical for the success of adoptive cell therapy (ACT). Unfortunately, only a small fraction of transferred cells home to solid tumors. Adhesive ligand-receptor interactions have been implicated in CD8 + T cell homing; however, there is a lack of understanding of how CD8 + T cells interact with tumor vasculature-expressed adhesive ligands under the influence of hemodynamic flow.
Here, the capacity of CD8 + T cells to home to melanomas is modeled ex vivo using an engineered microfluidic device that recapitulates the hemodynamic microenvironment of the tumor vasculature. Adoptively transferred CD8 + T cells with enhanced adhesion in flow in vitro and tumor homing in vivo improve tumor control by ACT in combination with immune checkpoint blockade.
These results show that engineered microfluidic devices can model the microenvironment of the tumor vasculature to identify subsets of T cells with enhanced tumor infiltrating capabilities, a key limitation in ACT.
论文信息
- 作者
- Camargo CP、Muhuri AK、Alapan Y、Sestito LF、Khosla M、Manspeaker MP、Smith AS、Paulos CM
- 第一作者单位
- George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA; Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332, USA.United States
- 通讯作者单位
- George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA; Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332, USA; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, USA; Winship Cancer Institute, Emory University, Atlanta, GA 30332, USA. Electronic address: susan.thomas@gatech.edu.United States
- 文献类型
- 美国 NIH 资助研究 · 美国政府（非公共卫生署）资助研究
- 期刊
- Cell reports2023 Mar 28
- 原文标识
- PubMed 36848287 · DOI 10.1016/j.celrep.2023.112175
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