Role of endoplasmic reticulum (ER) stress induced immunogenic lipids in cancer immunotherapy

The unfolded protein response is a conserved signalling pathway which aims to maintain cellular

homeostasis under conditions which promote endoplasmic reticulum (ER) stress. Both protein and

lipid biosynthesis are hallmark responses of the UPR whereas failure to restore cellular

homeostasis during UPR is widely acknowledged to promote inflammation and tumorigenesis. A

specialized subset of T cells called Natural Killer T (NKT) cells recognize glycolipids generated in

immune cells and produce immunodulatory cytokines and chemokines following activation.

Importantly, NKT cell activation is vital for adequate immune surveillance and intra-tumoral NKT

cell accumulation is associated with better prognosis. The aim of the current project proposal is

the identification of lipids generated in cells undergoing ER stress, the mechanisms by which UPRinduced

lipids bind to the antigen-presenting molecule CD1d and drive NKT cell activation. These

immunogenic lipids generated in cells during UPR will be evaluated for immunotherapy to combat

various tumors.