Alternatively spliced NKp30 isoforms affect the prognosis of gastrointestinal stromal tumors

Nat Med. 2011 Jun;17(6):700-7. doi: 10.1038/nm.2366. Epub 2011 May 8.


The natural killer (NK) cell receptor NKp30 is involved in the recognition of tumor and dendritic cells (DCs). Here we describe the influence of three NKp30 splice variants on the prognosis of gastrointestinal sarcoma (GIST), a malignancy that expresses NKp30 ligands and that is treated with NK-stimulatory KIT tyrosine kinase inhibitors. Healthy individuals and those with GIST show distinct patterns of transcription of functionally different NKp30 isoforms. In a retrospective analysis of 80 individuals with GIST, predominant expression of the immunosuppressive NKp30c isoform (over the immunostimulatory NKp30a and NKp30b isoforms) was associated with reduced survival of subjects, decreased NKp30-dependent tumor necrosis factor-α (TNF-α) and CD107a release, and defective interferon-γ (IFN-γ) and interleukin-12 (IL-12) secretion in the NK-DC cross-talk that could be restored by blocking of IL-10. Preferential NKp30c expression resulted partly from a single-nucleotide polymorphism at position 3790 in the 3' untranslated region of the gene encoding NKp30. The genetically determined NKp30 status predicts the clinical outcomes of individuals with GIST independently from KIT mutation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing / genetics*
  • Alternative Splicing / physiology
  • Cell Line, Tumor
  • Gastrointestinal Stromal Tumors / diagnosis
  • Gastrointestinal Stromal Tumors / genetics*
  • Gastrointestinal Stromal Tumors / physiopathology
  • Humans
  • Interferon-gamma / physiology
  • Interleukin-12 / physiology
  • Killer Cells, Natural / physiology
  • Lysosomal-Associated Membrane Protein 1 / physiology
  • Natural Cytotoxicity Triggering Receptor 3 / genetics*
  • Natural Cytotoxicity Triggering Receptor 3 / physiology
  • Polymorphism, Single Nucleotide / genetics
  • Prognosis
  • Protein Isoforms
  • Proto-Oncogene Proteins c-kit / genetics
  • Proto-Oncogene Proteins c-kit / physiology
  • Tumor Necrosis Factor-alpha / physiology


  • Lysosomal-Associated Membrane Protein 1
  • NCR3 protein, human
  • Natural Cytotoxicity Triggering Receptor 3
  • Protein Isoforms
  • Tumor Necrosis Factor-alpha
  • Interleukin-12
  • Interferon-gamma
  • Proto-Oncogene Proteins c-kit