ArticleScience advances2024
The nuclear export protein XPO1 provides a peptide ligand for natural killer cells.
Article in Science advances, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Protein language models accurately predict polymorphic peptide-modulated NK cell receptor-HLA class I interaction strengths.Science advances · 2026Article
- The XPO1 Inhibitor Eltanexor Modulates the Wnt/β-Catenin Signaling Pathway to Reduce Colorectal Cancer Tumorigenesis.Cancer research communications · 2025Article
- XPO1 as a key regulator in small cell lung cancer: mechanisms, biomarkers, and therapeutic implications.Cancer biology & medicine · 2025Article
- NK-cell cytotoxicity toward pluripotent stem cells and their neural progeny: impacts of activating and inhibitory receptors and KIR/HLA mismatch.Stem cells (Dayton, Ohio) · 2025Article
- Peptide-specific natural killer cell receptors.Oxford open immunology · 2025Review
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Authors and funding
17 authors.
Funding
Abstract
XPO1 (Exportin-1/CRM1) 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 anticancer 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 human leukocyte antigen-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 recognized by NK cells that offers an opportunity for a personalized approach to NK cell therapy for solid tumors.
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Registered trials
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