Dissimilar anti-tumour reactions induced by tumour cells engineered with the interleukin-2 or interleukin-15 gene in nude mice

J Pathol. 2000 Jun;191(2):193-201. doi: 10.1002/(SICI)1096-9896(200006)191:2<193::AID-PATH602>3.0.CO;2-4.


Interleukin (IL)-15 shares immuno-stimulatory properties with IL-2 and is a potent inducer of natural killer (NK) cell function. The major histocompatibility complex (MHC) class I-negative human small cell lung cancer (SCLC) cell line N592, engineered to express a modified IL-15 cDNA (N592/IL-15), secreted biologically active IL-15 (300-500 pg/ml), capable of boosting T-cell proliferation and NK activity 'in vitro'. The effect of IL-15 gene transfer on natural immunity 'in vivo' was assessed by xenotransplants in nude mice and compared with that of the IL-2 gene. N592 cells engineered with IL-2 (N592/IL-2) were promptly rejected, while N592/IL-15 displayed a significant delay in tumour growth and a slightly reduced take rate. However, in NK-depleted nude mice, N592/IL-15 displayed the same growth kinetics as unmodified N592 cells, and N592/IL-2 grew with slightly reduced kinetics. An impressive reactive cell infiltration, consisting mainly of macrophages and granulocytes, was associated with N592/IL-2 tumour rejection, while a more evident recruitment of NK cells was found in N592/IL-15 tumours. In both N592 transfected tumours, we found expression of chemoattractant molecules, such as granulocyte macrophage-colony stimulating factor (GM-CSF) and monocyte chemoattractant protein (MCP)-1, while macrophage inflammatory protein (MIP)-2 was produced by endothelial cells only in N592/IL-2 tumours. In this tumour, very few and severely damaged microvessels were found, while microvessels were numerous in N592/IL-15 tumours. The potent recruitment of NK cells mediated by IL-15 gene transfer suggests its possible therapeutic use in tumours lacking MHC class I.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Small Cell / genetics
  • Chemokine CCL2 / analysis
  • Female
  • Gene Transfer Techniques
  • Genes, MHC Class I / immunology
  • Graft Rejection / genetics
  • Graft Rejection / immunology
  • Granulocyte-Macrophage Colony-Stimulating Factor / analysis
  • Humans
  • Immunity, Innate / genetics*
  • Interleukin-15 / genetics*
  • Interleukin-2 / genetics*
  • Killer Cells, Natural / immunology
  • Lung Neoplasms / genetics
  • Macrophage Inflammatory Proteins / analysis
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Tumor Cells, Cultured


  • Chemokine CCL2
  • Interleukin-15
  • Interleukin-2
  • Macrophage Inflammatory Proteins
  • Granulocyte-Macrophage Colony-Stimulating Factor