Department of Mechanical Engineering, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea.
National Creative Research Initiatives Center, Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea.
ACS Biomater Sci Eng. 2021 Mar 8;7(3):1230-1241. doi: 10.1021/acsbiomaterials.0c01542. Epub 2021 Feb 14.
Fas ligand (FasL, CD178) is known to bind to its receptor (Fas, CD95) and mediate cellular apoptosis to maintain immune homeostasis. Recently, it has been recognized that tumor cells and their microenvironments allow an adjacent vascular endothelium to express the FasL on its cell membrane, utilizing the endothelium as an immune barrier to kill antitumor cytotoxic T cells. Here, a microfluidic tumor vasculature model is presented, which enables the recapitulation of an endothelial immune barrier expressing FasL. The in vitro three-dimensional model replicates enhanced endothelial FasL expression under the hypoxic tumor microenvironment. Apoptosis rates of FasL-susceptible target cells are augmented under the microenvironment with upregulated FasL but are consequently abrogated by administrations of pharmacological inhibitions, FasL-Fas blockades. The microfluidic system suggests its promising applications in elucidating complex immunosuppressive mechanisms of the tumor microenvironment and screening of cell-mediated immunotherapies as a preclinical model.
Fas 配体（FasL，CD178）已知可与其受体（Fas，CD95）结合，并介导细胞凋亡以维持免疫平衡。最近，人们已经认识到肿瘤细胞及其微环境允许相邻的血管内皮细胞在其细胞膜上表达 FasL，利用内皮细胞作为免疫屏障来杀死抗肿瘤细胞毒性 T 细胞。在这里，提出了一种微流控肿瘤血管模型，该模型能够重现表达 FasL 的内皮免疫屏障。该体外三维模型复制了在缺氧肿瘤微环境下增强的内皮 FasL 表达。在 FasL 上调的微环境下，FasL 易感靶细胞的凋亡率增加，但随后通过给予药理抑制、FasL-Fas 阻断而被消除。该微流控系统表明其在阐明肿瘤微环境中复杂的免疫抑制机制以及筛选细胞介导的免疫疗法方面具有广阔的应用前景，可作为临床前模型。
