Natural Killer Cells Control Tumor Growth by Sensing a Growth Factor.
Natural Killer Cells Control Tumor Growth by Sensing a Growth Factor.
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DOI：
10.1016/j.cell.2017.11.037
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发表时间：
2018-01-25
期刊：
影响因子：
64.5
通讯作者：
Colonna M
中科院分区：
文献类型：
--
作者：
Barrow AD;Edeling MA;Trifonov V;Luo J;Goyal P;Bohl B;Bando JK;Kim AH;Walker J;Andahazy M;Bugatti M;Melocchi L;Vermi W;Fremont DH;Cox S;Cella M;Schmedt C;Colonna M
许多肿瘤产生血小板衍生生长因子（PDGF）-DD，其通过自分泌和旁分泌PDGFRβ信号传导促进细胞增殖、上皮-间质转化、基质反应和血管生成。通过筛选分泌组文库，我们发现由NCR 2编码并在自然杀伤（NK）细胞和先天淋巴细胞上表达的人免疫受体NKp 44识别PDGF-DD。PDGF-DD与NKp 44的结合触发NK细胞分泌IFN-γ和TNF-α，诱导肿瘤细胞生长停滞。PDGF-DD诱导的细胞因子的独特转录特征和肿瘤细胞周期基因的下调与胶质母细胞瘤中的NCR 2表达和更高的存活率相关。与对照小鼠相比，小鼠NK细胞中的NKp 44表达更有效地控制了表达PDGF-DD的肿瘤的传播，抑制性受体CD 96或CpG寡核苷酸治疗的阻断增强了这一效果。因此，虽然癌细胞产生PDGF-DD支持肿瘤生长和基质反应，但它同时激活对肿瘤扩张的先天免疫应答。由多种类型的肿瘤表达的生长因子PDGF-DD是人NK细胞受体NKp 44的刺激配体。
Many tumors produce platelet-derived growth factor (PDGF)-DD, which promotes cellular proliferation, epithelial-mesenchymal transition, stromal reaction, and angiogenesis through autocrine and paracrine PDGFRβ signaling. By screening a secretome library, we found that the human immunoreceptor NKp44 encoded by NCR2 and expressed on natural killer (NK) cells and innate lymphoid cells recognizes PDGF-DD. PDGF-DD engagement of NKp44 triggered NK cell secretion of IFN-γ and TNF-α that induced tumor cell growth arrest. A distinctive transcriptional signature of PDGF-DD-induced cytokines and the downregulation of tumor cell cycle genes correlated with NCR2 expression and greater survival in glioblastoma. NKp44 expression in mouse NK cells controlled the dissemination of tumors expressing PDGF-DD more effectively than control mice, an effect enhanced by blockade of the inhibitory receptor CD96 or CpG-oligonucleotide treatment. Thus, whilst cancer cell production of PDGF-DD supports tumor growth and stromal reaction, it concomitantly activates innate immune responses to tumor expansion. The growth factor PDGF-DD, expressed by multiple types of tumor, is a stimulatory ligand for human NK cell receptor NKp44.
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影响因子：
64.8
作者：
Cella, Marina;Fuchs, Anja;Vermi, William;Facchetti, Fabio;Otero, Karel;Lennerz, Jochen K. M.;Doherty, Jason M.;Mills, Jason C.;Colonna, Marco
通讯作者：
Colonna, Marco
DOI：
10.1073/pnas.0914019107
发表时间：
2010-02-23
影响因子：
11.1
作者：
Gonzalez, Rodolfo;Jennings, Lori L.;Lesley, Scott A.
通讯作者：
Lesley, Scott A.
影响因子：
5.4
作者：
Ho, Joanna W.;Hershkovitz, Oren;Porgador, Angel
通讯作者：
Porgador, Angel
影响因子：
21.3
作者：
Bergsten, E;Uutela, M;Eriksson, U
通讯作者：
Eriksson, U
影响因子：
9.8
作者：
Ahola-Olli, Ari V.;Wurtz, Peter;Raitakari, Olli T.
通讯作者：
Raitakari, Olli T.