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

Using a mouse model in which tumors show a growth-regression-recurrence pat tern, we investigated the mechanisms for down-regulation of cytotoxic T lym phocyte-mediated tumor immunosurveillance. We found that interleukin 4 rece ptor (IL-4R) knockout and downstream signal transducer and activator of tra nscription 6 (STAT6) knockout, but not IL-4 knockout, mice resisted tumor r ecurrence, which implicated IL-13, the only other cytokine that uses the IL -4R-STAT6 pathway,We confirmed this by IL-13 inhibitor (sIL-13R alpha2-Fc) treatment. Loss of natural killer T eel Is (NKT cells) in CDI 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 immunos urveillance. IL-13 inhibitors may prove to be a useful tool in cancer immun otherapy.