IL-12 enhances the natural killer cell cytokine response to Ab-coated tumor cells

被引:172
作者
Parihar, R
Dierksheide, J
Hu, Y
Carson, WE
机构
[1] Ohio State Univ, Coll Med, Dept Surg, Columbus, OH 43210 USA
[2] Ohio State Univ, Coll Med, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA
[3] Ohio State Univ, Coll Med, Arthur G James Comprehens Canc Ctr, Columbus, OH 43210 USA
关键词
D O I
10.1172/JCI200215950
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
The anti-tumor activity of recombinant mAb's directed against tumor cell growth receptors has generally been considered to result from direct antiproliferative effects, the induction of apoptosis, or possibly Ab-dependent cellular cytotoxicity mediated against tumor targets. However, it remains unclear to what degree these mechanisms actually aid in the clearance of Ab-coated tumor cells in vivo. We show here that NK cells secrete a distinct profile of potent immunostimulatory cytokines in response to dual stimulation with Ab-coated tumor cells and IL-12. This response could not be duplicated by costimulation with other ILs and was significantly enhanced in the presence of monocytes. Cytokine production was dependent upon synergistic signals mediated by the activating receptor for the Fc portion of IgG (FcgammaRIII) and the IL-12 receptor expressed on NK cells. Coadministration of Ab-coated tumor cells and IL-12 to BALB/c mice resulted in enhanced circulating levels of NK cell-derived cytokines with the capacity to augment anti-tumor immunity. These findings suggest that, in addition to mediating cellular cytotoxicity and apoptosis, the anti-tumor activity of mAb's might also result from activation of a potent cytokine secretion program within immune effectors capable of recognizing mAb-coated targets.
引用
收藏
页码:983 / 992
页数:10
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