Identification and characterization of type 2 NKT ligands induced by endoplasmic reticulum stress in cancer immunotherapy

01 October 2020 → 17 September 2023
Research Foundation - Flanders (FWO)
Research disciplines
  • Medical and health sciences
    • Other basic sciences not elsewhere classified
Endoplasmic reticulum stress identification of novel type 2 NKT ligands cancer immunotherapy
Project description

During endoplasmic reticulum stress, both protein and lipid synthesis is modulated through a specialized signalling pathway called the unfolded protein response (UPR) in order to restore cellular homeostasis. If restoration fails, UPR mediated inflammatory responses will promote inflammation and tumourigenesis. Type 1 and Type 2 NKT cells are two broad classes of CD1d-restricted NKT cells, that recognize both self and non-self lipids as an antigen and produce immunomodulatory cytokines and chemokines upon activation. Type 2 NKT cells express diverse TCRs and have been shown to regulate immune surveillance and tumour immunity. The identity and immunogenic potential of most of these type 2 endogenous lipids remain unknown. This project will focus on the identification of UPR induced immunogenic lipids, the mechanism by which these immunogenic lipids bind to CD1d and drive type 2 NKT cell responses. Furthermore, we will synthesize these immunogenic lipids detected in stressed cells and carry out structure-function studies for potential use in cancer immunotherapy.