NKT cell-mediated repression of tumor immunosurveillance by IL-13 and the IL-4R-STAT6 pathway

Nat Immunol. 2000 Dec;1(6):515-20. doi: 10.1038/82771.


Using a mouse model in which tumors show a growth-regression-recurrence pattern, we investigated the mechanisms for down-regulation of cytotoxic T lymphocyte-mediated tumor immunosurveillance. We found that interleukin 4 receptor (IL-4R) knockout and downstream signal transducer and activator of transcription 6 (STAT6) knockout, but not IL-4 knockout, mice resisted tumor recurrence, which implicated IL-13, the only other cytokine that uses the IL-4R-STAT6 pathway. We confirmed this by IL-13 inhibitor (sIL-13R alpha 2-Fc) treatment. Loss of natural killer T cells (NKT cells) in CD1 knockout mice resulted in decreased IL-13 production and resistance to recurrence. Thus, NKT cells and IL-13, possibly produced by NKT cells and signaling through the IL-4R-STAT6 pathway, are necessary for down-regulation of tumor immunosurveillance. IL-13 inhibitors may prove to be a useful tool in cancer immunotherapy.

MeSH terms

  • Animals
  • Antigens, CD1 / genetics
  • Antigens, CD1 / metabolism
  • CD4 Antigens / metabolism
  • Cytokines / biosynthesis
  • Female
  • Immunotherapy
  • Interleukin-13 / antagonists & inhibitors
  • Interleukin-13 / metabolism
  • Killer Cells, Natural / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neoplasm Regression, Spontaneous / immunology
  • Neoplasms, Experimental / immunology*
  • Neoplasms, Experimental / metabolism
  • Neoplasms, Experimental / pathology
  • Receptors, Interleukin-4 / genetics
  • Receptors, Interleukin-4 / metabolism
  • Recurrence
  • STAT6 Transcription Factor
  • T-Lymphocytes / immunology*
  • Trans-Activators / genetics
  • Trans-Activators / metabolism


  • Antigens, CD1
  • CD4 Antigens
  • Cytokines
  • Interleukin-13
  • Receptors, Interleukin-4
  • STAT6 Transcription Factor
  • Stat6 protein, mouse
  • Trans-Activators