Engineered Tissues for Discovery, Industry and Medicine

免疫检查点阻断剂（ICBs）调节针对癌症的免疫反应，彻底改变了癌症治疗，但当肿瘤转移到肝脏时，ICBs的疗效很低1。这是一个巨大的挑战，因为肝脏是继发性肿瘤最常见的部位之一。此外，只有20%的原发性肝癌患者对免疫治疗有反应2。因此，肝脏微环境似乎是抑制肿瘤特异性反应的主要驱动因素，使癌症治疗效率降低。肝脏是一个致耐受性器官，肝窦内皮细胞（LSEC）排列在肝脏的细血管上，对致耐受性微环境做出关键贡献3。LSEC可以改变免疫细胞功能，并作为免疫细胞浸润到肝脏中的看门人，控制哪些免疫细胞亚群从循环中招募4。LSEC的重要性在组织再生和癌症过程中经常被忽视，我们有初步数据显示，人类肝内皮细胞被肿瘤微环境重新编程，并可能形成效应T细胞募集/激活的屏障。

Immune checkpoint blockers (ICBs) which regulates immune response against cancer have revolutionized cancer therapy, but the efficacy of ICBs is low when tumours metastasise to the liver1. This is a huge challenge since the liver is one of the commonest sites for secondary tumours. Furthermore, only 20% of primary liver cancer patients are responsive to immunotherapy2. The liver microenvironment therefore appears to be a major driver in suppressing tumour specific responses making cancer therapy less efficient.The liver is a tolerogenic organ with liver sinusoidal endothelial cells (LSEC), which line the fine blood vessels in the liver, making a critical contribution to the tolerogenic microenvironment3. LSEC can alter immune cell function and act as the gatekeeper to immune cell infiltration into the liver, controlling which immune cell subsets are recruited from the circulation4. The importance of LSEC is often overlooked during tissue regeneration and cancer, and we have pilot data showing that human liver endothelium is reprogrammed by the tumour microenvironment and likely to form a barrier to effector T cell recruitment/activation.