Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.
Nat Immunol. 2010 Nov;11(11):1030-8. doi: 10.1038/ni.1947. Epub 2010 Oct 10.
The potent tumoricidal activity of interleukin 12 (IL-12) is thought to be mediated by the activation and polarization of natural killer (NK) cells and T helper type 1 (T(H)1) cells, respectively. By systematic analysis of the IL-12-induced immune response to subcutaneous melanoma (B16), we found that tumor suppression was mediated independently of T lymphocytes or NK cells. IL-12 initiated local antitumor immunity by stimulating a subset of NKp46(+) lymphoid tissue-inducer (LTi) cells dependent on the transcription factor RORγt. The presence of these NKp46(+) LTi cells induced upregulation of adhesion molecules in the tumor vasculature and resulted in more leukocyte invasion. Thus, this innate cell type is responsive to IL-12 and is a powerful mediator of tumor suppression.
白细胞介素 12（IL-12）的强大肿瘤杀伤活性被认为分别通过自然杀伤（NK）细胞和辅助性 T 细胞 1（T(H)1）细胞的激活和极化来介导。通过对白细胞介素 12 诱导的皮下黑色素瘤（B16）免疫反应的系统分析，我们发现肿瘤抑制是独立于 T 淋巴细胞或 NK 细胞介导的。白细胞介素 12 通过刺激依赖于转录因子 RORγt 的一组 NKp46(+)淋巴组织诱导（LTi）细胞，启动局部抗肿瘤免疫。这些 NKp46(+) LTi 细胞的存在诱导肿瘤血管中黏附分子的上调，并导致更多白细胞浸润。因此，这种先天细胞类型对白细胞介素 12 有反应，是肿瘤抑制的强大介质。
