The nuclear export protein XPO1 provides a peptide ligand for natural killer cells

ABSTRACT: XPO1 is a nuclear export protein that is frequently overexpressed in cancer and functions as a driver of oncogenesis. Currently small molecules that target XPO1 are being used in the clinic as anti-cancer agents. We identify XPO1 as a target for natural killer (NK) cells. Using immunopeptidomics we have identified a peptide derived from XPO1 that can be recognized by the activating NK cell receptor KIR2DS2 in the context of HLA-C. The peptide can be endogenously processed and presented to activate NK cells specifically through this receptor. Although high XPO1 expression in cancer is commonly associated with a poor prognosis, we show that the outcome of specific cancers, such as hepatocellular carcinoma, can be substantially improved if there is concomitant evidence of NK cell infiltration. We thus identify XPO1 as a bona fide tumor antigen recognised by NK cells, that offers an opportunity for a personalized approach to NK cell therapy for solid tumors.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Liver

SUBMITTER: Ralf Schittenhelm  

LAB HEAD: Salim Khakoo

PROVIDER: PXD053264 | Pride | 2024-10-17

REPOSITORIES: Pride