Engineered Tissues for Discovery, Industry and Medicine

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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.