Elevated ER stress is detected in many cancers, including hepatocellular carcinoma (HCC). ER stress can lead
to altered lipid biosynthesis. A specialized subset of T cells called Natural Killer T (NKT) cells recognizes lipids
as antigens when they are presented by the non-classical MHC molecule CD1d and will produce
immunomodulatory cytokines and chemokines following activation. Importantly, NKT cell activation is vital for
adequate immune surveillance and intra-tumoral NKT cell accumulation is associated with a better prognosis.
The aim of this project proposal is to identify and characterize novel endogenous immunogenic lipids generated
by ER stress in the context of non-alcoholic steatohepatitis (NASH)-driven HCC. We anticipate that ER stressinduced
lipids will activate NKT cells, which will in turn lead to anti-tumoral immunity. These immunogenic lipids
generated during ER stress will be evaluated for NASH-driven HCC immunotherapy