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T细胞的CD28超激动剂激活诱导肿瘤细胞样代谢程序。

CD28 Superagonistic Activation of T Cells Induces a Tumor Cell-Like Metabolic Program.

作者信息

Thaventhiran Thilipan, Wong Wai, Alghanem Ahmad F, Alhumeed Naif, Aljasir Mohammad A, Ramsey Simeon, Sethu Swaminathan, Yeang Han Xian Aw, Chadwick Amy E, Cross Michael, Webb Steven D, Djouhri Laiche, Ball Christina, Stebbings Richard, Sathish Jean G

机构信息

1 Medical Research Council Centre for Drug Safety Science and Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, United Kingdom.

2 Inflammation and Remodeling, Pfizer Research Unit, Cambridge, Massachusetts.

出版信息

Monoclon Antib Immunodiagn Immunother. 2019 Apr;38(2):60-69. doi: 10.1089/mab.2018.0042.

DOI:10.1089/mab.2018.0042
PMID:31009338
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6634261/
Abstract

CD28 superagonist (CD28SA), a therapeutic immunomodulatory monoclonal antibody triggered rapid and exaggerated activation of CD4 effector memory T cells (T) in humans with unwanted serious adverse effects. It is well known that distinct metabolic programs determine the fate and responses of immune cells. In this study, we show that human CD4 T stimulated with CD28SA adopt a metabolic program similar to those of tumor cells with enhanced glucose utilization, lipid biosynthesis, and proliferation in hypoxic conditions. Identification of metabolic profiles underlying hyperactive T cell activation would provide a platform to test safety of immunostimulatory antibodies.

摘要

CD28超激动剂（CD28SA）是一种治疗性免疫调节单克隆抗体，可在人体中引发CD4效应记忆T细胞（T细胞）的快速且过度激活，并产生不良的严重副作用。众所周知，不同的代谢程序决定了免疫细胞的命运和反应。在本研究中，我们发现用CD28SA刺激的人类CD4 T细胞采用了类似于肿瘤细胞的代谢程序，在缺氧条件下增强了葡萄糖利用、脂质生物合成和增殖。确定过度活跃的T细胞激活背后的代谢谱将为测试免疫刺激抗体的安全性提供一个平台。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a7e/6634261/9b8102969b09/fig-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a7e/6634261/908f22904701/fig-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a7e/6634261/05ab090e8aa6/fig-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a7e/6634261/7cb80edd8f04/fig-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a7e/6634261/9b8102969b09/fig-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a7e/6634261/908f22904701/fig-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a7e/6634261/05ab090e8aa6/fig-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a7e/6634261/7cb80edd8f04/fig-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a7e/6634261/9b8102969b09/fig-4.jpg

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本文引用的文献

1
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2
Early TCR Signaling Induces Rapid Aerobic Glycolysis Enabling Distinct Acute T Cell Effector Functions.早期 TCR 信号诱导快速有氧糖酵解，从而实现独特的急性 T 细胞效应功能。
Cell Rep. 2018 Feb 6;22(6):1509-1521. doi: 10.1016/j.celrep.2018.01.040.
3
Metabolic Control of CD8 T Cell Fate Decisions and Antitumor Immunity.代谢控制 CD8 T 细胞命运决策和抗肿瘤免疫。
人肾近端小管上皮细胞在 CD4+T 细胞直接同种异体识别中的作用及其缺血再灌注的影响。
Int J Mol Sci. 2021 Feb 9;22(4):1733. doi: 10.3390/ijms22041733.
Trends Mol Med. 2018 Jan;24(1):30-48. doi: 10.1016/j.molmed.2017.11.005. Epub 2017 Dec 12.
4
The spectrum of T cell metabolism in health and disease.T 细胞代谢在健康和疾病中的图谱。
Nat Rev Immunol. 2018 Jan;18(1):19-34. doi: 10.1038/nri.2017.99. Epub 2017 Sep 25.
5
Metabolic Regulation of T Cell Longevity and Function in Tumor Immunotherapy.肿瘤免疫治疗中T细胞寿命和功能的代谢调控
Cell Metab. 2017 Jul 5;26(1):94-109. doi: 10.1016/j.cmet.2017.06.016.
6
T cell metabolism drives immunity.T细胞代谢驱动免疫。
J Exp Med. 2015 Aug 24;212(9):1345-60. doi: 10.1084/jem.20151159. Epub 2015 Aug 10.
7
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8
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