Ingram Jessica R, Dougan Michael, Rashidian Mohammad, Knoll Marko, Keliher Edmund J, Garrett Sarah, Garforth Scott, Blomberg Olga S, Espinosa Camilo, Bhan Atul, Almo Steven C, Weissleder Ralph, Lodish Harvey, Dougan Stephanie K, Ploegh Hidde L
Whitehead Institute for Biomedical Research, Cambridge, MA, 02142, USA.
Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, 02115, USA.
Nat Commun. 2017 Sep 21;8(1):647. doi: 10.1038/s41467-017-00799-8.
Programmed death ligand 1 (PD-L1) is expressed on a number of immune and cancer cells, where it can downregulate antitumor immune responses. Its expression has been linked to metabolic changes in these cells. Here we develop a radiolabeled camelid single-domain antibody (anti-PD-L1 VHH) to track PD-L1 expression by immuno-positron emission tomography (PET). PET-CT imaging shows a robust and specific PD-L1 signal in brown adipose tissue (BAT). We confirm expression of PD-L1 on brown adipocytes and demonstrate that signal intensity does not change in response to cold exposure or β-adrenergic activation. This is the first robust method of visualizing murine brown fat independent of its activation state.Current approaches to visualise brown adipose tissue (BAT) rely primarily on markers that reflect its metabolic activity. Here, the authors show that PD-L1 is expressed on brown adipocytes, does not change upon BAT activation, and that BAT volume in mice can be measured by PET-CT with a radiolabeled anti-PD-L1 antibody.
程序性死亡配体1（PD-L1）在多种免疫细胞和癌细胞上表达，它可下调抗肿瘤免疫反应。其表达与这些细胞的代谢变化有关。在此，我们开发了一种放射性标记的骆驼科单域抗体（抗PD-L1 VHH），以通过免疫正电子发射断层扫描（PET）追踪PD-L1的表达。PET-CT成像显示在棕色脂肪组织（BAT）中有强烈且特异的PD-L1信号。我们证实了棕色脂肪细胞上PD-L1的表达，并证明信号强度不会因冷暴露或β-肾上腺素能激活而改变。这是第一种不依赖于其激活状态来可视化小鼠棕色脂肪的可靠方法。目前可视化棕色脂肪组织（BAT）的方法主要依赖于反映其代谢活性的标志物。在此，作者表明PD-L1在棕色脂肪细胞上表达，在BAT激活时不会改变，并且小鼠的BAT体积可以用放射性标记的抗PD-L1抗体通过PET-CT进行测量。
