Cancer Res：卵巢癌肿瘤或用GD3来抑制抗肿瘤NK细胞的效应

近日，国际著名杂志Cancer Research在线刊登了德国伯恩大学研究者的最新研究成果“Molecular Identification of GD3 as a Suppressor of the Innate Immune Response in Ovarian Cancer，”文章中，研究者揭示了在卵巢癌中，新分子GD3可以作为先天免疫效应的一个抑制剂。

目前，卵巢癌是女性生殖器官常见的肿瘤之一，发病率仅次于子宫颈癌，对妇女生命带来了严重威胁。肿瘤通常发挥很复杂的机制来避免或者抑制机体免疫系统的识别，一种很典型的机制就是在肿瘤微环境中脱落神经节苷脂类，而且高浓度的神经节苷脂类和预后不良直接相关。

研究者Jonathan P. Schneck表示，在这项研究中，他们发现了神经节苷脂GD3，是从卵巢癌的极性脂质部分分离出来的，GD3可以作为抑制因子来抑制自然杀伤细胞NK细胞的天然免疫活性。

纯化后的GD3不管是在人类还是在小鼠的CD1d细胞中均具有高亲和力。CD1d参与了T细胞脂类抗原的呈递工作，纯化后的GD3可以结合至CD1d的抗原结合位点，更重要的是，体内试验表明GD3的操作可以抑制α-半乳糖神经酰胺诱导的NK细胞的活性。

总之，研究者的研究数据揭示了在肿瘤扩散的早期阶段，卵巢癌肿瘤或许用GD3来抑制抗肿瘤NK细胞的效应。

doi:10.1158/0008-5472.CAN-11-2695
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Molecular Identification of GD3 as a Suppressor of the Innate Immune Response in Ovarian Cancer

Tonya J. Webb1, Xiangming Li4, Robert L. Giuntoli II2, Pablo H.H. Lopez3, Christoph Heuser5, Ronald L. Schnaar3, Moriya Tsuji4, Christian Kurts5, Mathias Oelke1, and Jonathan P. Schneck1

Tumors often display mechanisms to avoid or suppress immune recognition. One such mechanism is the shedding of gangliosides into the local tumor microenvironment, and a high concentration of circulating gangliosides is associated with poor prognosis. In this study, we identify ganglioside GD3, which was isolated from the polar lipid fraction of ovarian cancer–associated ascites, as an inhibitory factor that prevents innate immune activation of natural killer T (NKT) cells. Purified GD3 displayed a high affinity for both human and mouse CD1d, a molecule involved in the presentation of lipid antigens to T cells. Purified GD3, as well as substances within the ascites, bound to the CD1d antigenic-binding site and did not require additional processing for its inhibitory effect on NKT cells. Importantly, in vivo administration of GD3 inhibited α-galactosylceramide (α-GalCer)-induced NKT cell activation in a dose-dependent manner. These data therefore indicate that ovarian cancer tumors may use GD3 to inhibit the antitumor NKT cell response as an early mechanism of tumor immune evasion. Cancer Res; 72(15); 3744–52. ©2012 AACR.