近日,，國際著名雜志Cancer Research在線刊登了德國伯恩大學(xué)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可以作為先天免疫效應(yīng)的一個抑制劑,。
目前，卵巢癌是女性生殖器官常見的腫瘤之一,，發(fā)病率僅次于子宮頸癌,，對婦女生命帶來了嚴重威脅。腫瘤通常發(fā)揮很復(fù)雜的機制來避免或者抑制機體免疫系統(tǒng)的識別,，一種很典型的機制就是在腫瘤微環(huán)境中脫落神經(jīng)節(jié)苷脂類,，而且高濃度的神經(jīng)節(jié)苷脂類和預(yù)后不良直接相關(guān)。
研究者Jonathan P. Schneck表示,，在這項研究中,，他們發(fā)現(xiàn)了神經(jīng)節(jié)苷脂GD3，是從卵巢癌的極性脂質(zhì)部分分離出來的,，GD3可以作為抑制因子來抑制自然殺傷細胞NK細胞的天然免疫活性,。
純化后的GD3不管是在人類還是在小鼠的CD1d細胞中均具有高親和力,。CD1d參與了T細胞脂類抗原的呈遞工作，純化后的GD3可以結(jié)合至CD1d的抗原結(jié)合位點,，更重要的是,，體內(nèi)試驗表明GD3的操作可以抑制α-半乳糖神經(jīng)酰胺誘導(dǎo)的NK細胞的活性。
總之,，研究者的研究數(shù)據(jù)揭示了在腫瘤擴散的早期階段,，卵巢癌腫瘤或許用GD3來抑制抗腫瘤NK細胞的效應(yīng)。（生物谷Bioon.com）
doi:10.1158/0008-5472.CAN-11-2695
PMC:
PMID:
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.
