IL-12 initiates tumor rejection via lymphoid tissue-inducer cells bearing the natural cytotoxicity receptor NKp46
IL-12 initiates tumor rejection via lymphoid tissue-inducer cells bearing the natural cytotoxicity receptor NKp46
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DOI：
10.1038/ni.1947
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发表时间：
2010-11-01
影响因子：
30.5
通讯作者：
Becher, Burkhard
中科院分区：
文献类型：
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作者：
Eisenring, Maya;vom Berg, Johannes;Becher, Burkhard
白细胞介素 12 (IL-12) 的有效杀肿瘤活性被认为是分别通过自然杀伤 (NK) 细胞和 1 型辅助 T (T(H)1) 细胞的激活和极化介导的。通过系统分析 IL-12 诱导的皮下黑色素瘤 (B16) 免疫反应，我们发现肿瘤抑制的介导独立于 T 淋巴细胞或 NK 细胞。 IL-12 通过刺激依赖于转录因子 ROR gamma t 的 NKp46(+) 淋巴组织诱导 (LTi) 细胞子集来启动局部抗肿瘤免疫。这些 NKp46(+) LTi 细胞的存在诱导肿瘤血管系统中粘附分子的上调，并导致更多的白细胞侵袭。因此，这种先天细胞类型对 IL-12 有反应，是肿瘤抑制的强大介质。
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 ROR gamma t. 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.