Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, USA.
Committee on Cancer Biology, The University of Chicago, Chicago, USA.
Sci Rep. 2017 Jul 19;7(1):5790. doi: 10.1038/s41598-017-05556-x.
Fatty acid (FA) metabolism directly influences the functional capabilities of T cells in tumor microenvironments. Thus, developing tools to interrogate FA-uptake by T cell subsets is important for understanding tumor immunosuppression. Herein, we have generated a novel FA-Qdot 605 dye conjugate with superior sensitivity and flexibility to any of the previously commercially available alternatives. For the first time, we demonstrate that this nanoparticle can be used as a specific measure of fatty acid uptake by T cells both in-vitro and in-vivo. Flow cytometric analysis shows that both the location and activation status of T cells determines their FA uptake. Additionally, CD4+ Foxp3+ regulatory T cells (Tregs) uptake FA at a higher rate than effector T cell subsets, supporting the role of FA metabolism for Treg function. Furthermore, we are able to simultaneously detect glucose and fatty acid uptake directly within the tumor microenvironment. Cumulatively, our results suggest that this novel fluorescent probe is a powerful tool to understand FA utilization within the tumor, thereby providing an unprecedented opportunity to study T cell FA metabolism in-vivo.
脂肪酸（FA）代谢直接影响肿瘤微环境中 T 细胞的功能能力。因此，开发用于检测 T 细胞亚群摄取 FA 的工具对于理解肿瘤免疫抑制至关重要。在此，我们生成了一种新型的 FA-Qdot 605 染料缀合物，与以前任何市售的替代品相比，其灵敏度和灵活性都有所提高。我们首次证明，这种纳米颗粒可以作为 T 细胞在体外和体内摄取脂肪酸的特异性指标。流式细胞术分析表明，T 细胞的位置和激活状态决定了它们对 FA 的摄取。此外，CD4+Foxp3+调节性 T 细胞（Tregs）摄取 FA 的速度比效应 T 细胞亚群更快，这支持了 FA 代谢对 Treg 功能的作用。此外，我们能够直接在肿瘤微环境中同时检测葡萄糖和脂肪酸的摄取。总的来说，我们的结果表明，这种新型荧光探针是理解肿瘤内 FA 利用的有力工具，从而为研究体内 T 细胞 FA 代谢提供了前所未有的机会。
