PDF(Pubmed)
Abstract：
Whether and how the reactive oxygen species generated by hepatic stellate cells (HSCs) promote immune evasion of hepatocellular carcinoma (HCC) remains mysterious. Therefore, investigating the function of superoxide anion (O2•-), the firstly generated reactive oxygen species, during the immune evasion become necessary. In this work, we establish a novel in situ imaging method for visualization of O2•- changes in HSCs based on a new two-photon fluorescence probe TPH. TPH comprises recognition group for O2•- and HSCs targeting peptides. We observe that O2•- in HSCs gradually rose, impairing the infiltration of CD8+ T cells in HCC mice. Further studies reveal that the cyclin-dependent kinase 4 is deactivated by O2•-, and then cause the up-regulation of PD-L1. Our work provides molecular insights into HSC-mediated immune evasion of HCC, which may represent potential targets for HCC immunotherapy.
摘要：
肝星状细胞（HSC）产生的活性氧是否以及如何促进肝细胞癌（HCC）的免疫逃避仍然是个谜。因此,研究超氧阴离子(O2·-)的功能，首先产生的活性氧，在免疫逃避成为必要。在这项工作中,我们建立了一种基于新型双光子荧光探针TPH的原位成像方法，用于可视化HSCs中O2·-的变化。TPH包含O2·-和HSC靶向肽的识别基团。我们观察到HSC中的O2•-逐渐上升，损伤肝癌小鼠CD8+T细胞的浸润。进一步的研究表明，细胞周期蛋白依赖性激酶4被O2·-失活，然后引起PD-L1的上调。我们的工作提供了HSC介导的HCC免疫逃避的分子见解，这可能是肝癌免疫治疗的潜在靶点。
