γδ T 细胞调节小细胞肺癌中的抗肿瘤免疫
γδ T cells modulate anti-tumor immunity in small cell lung cancer.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
糖酵解抑制影响用于过继细胞治疗的 Vγ9Vδ2 T 细胞的增殖和细胞毒性
英文原题：Glycolysis inhibition affects proliferation and cytotoxicity of Vγ9Vδ2 T cells expanded for adoptive cell therapy.
查看英文原题
Glycolysis inhibition affects proliferation and cytotoxicity of Vγ9Vδ2 T cells expanded for adoptive cell therapy.
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研究概要
这些发现为进一步研究通过调控 Vγ9Vδ2 T 细胞代谢来改善 ACT 结局奠定了基础。
研究思路结论见上方概要
背景
Vγ9Vδ2 T细胞正在被研究作为癌症过继细胞治疗（ACT）的替代效应细胞。尽管体外实验结果令人鼓舞，但早期临床研究中的抗肿瘤疗效低于预期，这可能归因于肿瘤和免疫细胞代谢在肿瘤微环境中竞争相同营养物质的复杂相互作用。
方法
为了弥补关于γδ T细胞代谢知识的不足，我们研究了扩增25天的Vγ9Vδ2 T细胞的代谢表型及其与功能之间的相互关联。
结果
我们发现，Vγ9Vδ2 T 细胞表现出静息代谢，在 Seahorse 检测中同时利用糖酵解和氧化磷酸化（OXPHOS）产生能量。T 细胞受体激活后，这两条通路均上调，使用代谢抑制剂进行抑制表明 Vγ9Vδ2 T 细胞的增殖依赖于糖酵解和磷酸戊糖途径。在无葡萄糖条件下证实了增殖对葡萄糖的依赖性。糖酵解抑制降低了针对恶性黑色素瘤的细胞毒性，但 OXPHOS 抑制未降低。
展开英文摘要原文
METHODS
To contribute to the scarce knowledge regarding gamma delta T-cell metabolism, we investigated the metabolic phenotype of 25-day-expanded Vγ9Vδ2 T cells and how it is intertwined with functionality.
RESULTS
We found that Vγ9Vδ2 T cells displayed a quiescent metabolism, utilizing both glycolysis and oxidative phosphorylation (OXPHOS) for energy production, as measured in Seahorse assays. Upon T-cell receptor activation, both pathways were upregulated, and inhibition with metabolic inhibitors showed that Vγ9Vδ2 T cells were dependent on glycolysis and the pentose phosphate pathway for proliferation. The dependency on glucose for proliferation was confirmed in glucose-free conditions. Cytotoxicity against malignant melanoma was reduced by glycolysis inhibition but not OXPHOS inhibition.
CONCLUSIONS
These findings lay the groundwork for further studies on manipulation of Vγ9Vδ2 T-cell metabolism for improved ACT outcome.
论文信息
- 作者
- Aehnlich P、Santiago MV、Dam SH、Saló SF、Rahbech A、Olsen LR、Thor Straten P、Desler C
- 第一作者单位
- National Center for Cancer Immune Therapy, Department of Oncology, Copenhagen University Hospital Herlev, Herlev, Denmark; Department of Clinical Science, University of Bergen, Bergen, Norway.Denmark
- 通讯作者单位
- National Center for Cancer Immune Therapy, Department of Oncology, Copenhagen University Hospital Herlev, Herlev, Denmark. Electronic address: gitte.holmen.olofsson@regionh.dk.Denmark
- 期刊
- Cytotherapy2024 Sep
- 原文标识
- PubMed 38775775 · DOI 10.1016/j.jcyt.2024.04.072