NKp46 Receptor-Mediated Interferon-γ Production by Natural Killer Cells Increases Fibronectin 1 to Alter Tumor Architecture and Control Metastasis.
NKp46 Receptor-Mediated Interferon-γ Production by Natural Killer Cells Increases Fibronectin 1 to Alter Tumor Architecture and Control Metastasis.
复制标题
DOI：
10.1016/j.immuni.2018.01.010
复制
发表时间：
2018-02-20
期刊：
影响因子：
32.4
通讯作者：
Mandelboim O
中科院分区：
文献类型：
--
作者：
Glasner A;Levi A;Enk J;Isaacson B;Viukov S;Orlanski S;Scope A;Neuman T;Enk CD;Hanna JH;Sexl V;Jonjic S;Seliger B;Zitvogel L;Mandelboim O
自然杀伤细胞（NK）是先天淋巴样细胞，它们在人类肿瘤中的存在与较好的预后相关。然而，NK细胞在体内控制肿瘤的机制尚不清楚。在这里，我们使用人类和小鼠的反射共聚焦显微镜（RCM）成像来观察体内肿瘤的结构。我们证明NK细胞受体NKp46（人类）和Ncr1（小鼠）的信号传导诱导肿瘤内NK细胞分泌干扰素-γ (IFN-γ)。NKp46-和ncr1介导的IFN-γ产生导致肿瘤中细胞外基质蛋白纤维连接蛋白1 （FN1）的表达增加，从而改变原发肿瘤结构并导致转移形成减少。向荷瘤小鼠注射IFN-γ或在小鼠NK细胞中转基因过表达Ncr1可减少转移形成。因此，我们已经确定了NK细胞介导的体内转移控制机制，这可能有助于开发依赖NK细胞的癌症治疗方法。
Natural killer (NK) cells are innate lymphoid cells, and their presence within human tumors correlates with better prognosis. However, the mechanisms by which NK cells control tumorsin vivoare unclear. Here, we used reflectance confocal microscopy (RCM) imaging in humans and in mice to visualize tumor architecturein vivo. We demonstrated that signaling via the NK cell receptor NKp46 (human) and Ncr1 (mouse) induced interferon-γ (IFN-γ) secretion from intratumoral NK cells. NKp46- and Ncr1-mediated IFN-γ production led to the increased expression of the extracellular matrix protein fibronectin 1 (FN1) in the tumors, which altered primary tumor architecture and resulted in decreased metastases formation. Injection of IFN-γ into tumor-bearing mice or transgenic overexpression of Ncr1 in NK cells in mice resulted in decreased metastasis formation. Thus, we have defined a mechanism of NK cell-mediated control of metastasesin vivothat may help develop NK cell-dependent cancer therapies.
影响因子：
32.4
作者：
Glasner, Ariella;Levi, Assi;Mandelboim, Ofer
通讯作者：
Mandelboim, Ofer