Natural killer T cells infiltrate neuroblastomas expressing the chemokine CCL2.
Natural killer T cells infiltrate neuroblastomas expressing the chemokine CCL2.
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DOI：
10.1084/jem.20031462
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发表时间：
2004-05-03
期刊：
影响因子：
--
通讯作者：
Seeger RC
中科院分区：
文献类型：
--
作者：
Metelitsa LS;Wu HW;Wang H;Yang Y;Warsi Z;Asgharzadeh S;Groshen S;Wilson SB;Seeger RC
CD 1d-限制性Vα24-Jα18-不变的自然杀伤T细胞（iNKT）在肿瘤免疫中具有潜在的重要性。然而，关于它们在肿瘤中的定位知之甚少。我们使用TaqMan®逆转录聚合酶链反应和免疫荧光显微镜分析了98例来自转移性疾病（4期）患者的未经治疗的原发性神经母细胞瘤的肿瘤浸润性iNKT。52个肿瘤（53%）含有iNKT，iNKT+和iNKT−肿瘤的寡核苷酸微阵列分析显示，前者表达更高水平的CCL 2/MCP-1，CXCL 12/SDF-1，CCL 5/RANTES和CCL 21/SLC。8个测试的神经母细胞瘤细胞系分泌一系列CCL 2（0-21.6 ng/ml），少量CXCL 12（≤0.1 ng/ml），并且未检测到CCL 5或CCL 21。与自然杀伤细胞和来自血液的T细胞相比，iNKT更频繁地表达CCL 2的受体CCR 2（P < 0.001）。产生CCL 2的神经母细胞瘤细胞系的上清液诱导来自患者和正常成人血液的iNKT的体外迁移;这被抗CCL 2单克隆抗体废除。发现肿瘤的CCL 2表达与MYCN原癌基因扩增和表达呈负相关（r = 0.5，P < 0.001），并且MYCN高/CCL 2低表达准确地预测了iNKT的缺乏（P < 0.001）。总之，iNKT以CCL 2依赖性方式向神经母细胞瘤细胞迁移，优先浸润表达CCL 2的MYCN非扩增肿瘤。
CD1d-restricted Vα24-Jα18–invariant natural killer T cells (iNKTs) are potentially important in tumor immunity. However, little is known about their localization to tumors. We analyzed 98 untreated primary neuroblastomas from patients with metastatic disease (stage 4) for tumor-infiltrating iNKTs using TaqMan® reverse transcription polymerase chain reaction and immunofluorescent microscopy. 52 tumors (53%) contained iNKTs, and oligonucleotide microarray analysis of the iNKT+ and iNKT− tumors revealed that the former expressed higher levels of CCL2/MCP-1, CXCL12/SDF-1, CCL5/RANTES, and CCL21/SLC. Eight tested neuroblastoma cell lines secreted a range of CCL2 (0–21.6 ng/ml), little CXCL12 (≤0.1 ng/ml), and no detectable CCL5 or CCL21. CCR2, the receptor for CCL2, was more frequently expressed by iNKT compared with natural killer and T cells from blood (P < 0.001). Supernatants of neuroblastoma cell lines that produced CCL2 induced in vitro migration of iNKTs from blood of patients and normal adults; this was abrogated by an anti-CCL2 monoclonal antibody. CCL2 expression by tumors was found to inversely correlate with MYCN proto-oncogene amplification and expression (r = 0.5, P < 0.001), and MYCN-high/CCL2-low expression accurately predicted the absence of iNKTs (P < 0.001). In summary, iNKTs migrate toward neuroblastoma cells in a CCL2-dependent manner, preferentially infiltrating MYCN nonamplified tumors that express CCL2.
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影响因子：
45.3
作者：
Schmidt, ML;Lukens, JN;Matthay, KK
通讯作者：
Matthay, KK
DOI：
10.1073/pnas.011404098
发表时间：
2001-01-02
影响因子：
11.1
作者：
Li, C;Wong, WH
通讯作者：
Wong, WH
影响因子：
4.4
作者：
Nesbit, M;Schaider, H;Herlyn, M
通讯作者：
Herlyn, M
DOI：
10.1097/00019606-199212000-00002
发表时间：
1992-12-01
期刊：
Diagnostic molecular pathology : the American journal of surgical pathology, part B
影响因子：
--
作者：
Crabbe, D C;Peters, J;Seeger, R C
通讯作者：
Seeger, R C
影响因子：
20.3
作者：
Kim, CH;Johnston, B;Butcher, EC
通讯作者：
Butcher, EC