When cancer cells leaves their hometown to colonize a distant organ through the bloodstream, the liver is one of their most common destination. Abundant innate immune cells reside inside the liver vasculature, including Kupffer cells, NK and NKT cells, how these cells orchestrate to perform an immune surveillance program in situ against invading cancer cells remains largely unknown but can be targeted for preventing liver metastasis in pre-metastatic cancer patients. By using the cutting-edge intravital imaging, we are currently studying the cellular interactions of these immune cells with metastatic cancer cells to dissect their immune surveillance functions in vivo and in real time. On the other hand, because patients with established liver metastasis are often resistant to T cell based cancer immunotherapy, as well as our findings that the liver favors induction of T cell tolerance rather than immunity (Zeng Z. et al., J Exp Med, 2016; Zeng Z et al., J Immunol 2013). we will investigate the immune evading mechanisms during liver metastasis with a particular focus on T cell tolerance.
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