近日，復(fù)旦大學(xué)上海醫(yī)學(xué)院免疫學(xué)系儲(chǔ)以微教授課題組經(jīng)３年潛心研究發(fā)現(xiàn),，有一種從細(xì)菌中提取的名叫“BLP”的細(xì)菌脂蛋白,，一旦與存在于T淋巴細(xì)胞表面的TLR-2受體“一對(duì)一配接”后，可以調(diào)動(dòng)一群具有殺傷性T淋巴細(xì)胞明顯增強(qiáng)其殺傷癌細(xì)胞的能力,，同時(shí),，這種“一對(duì)一配接”還可以削弱和抑制另外一群調(diào)節(jié)性T淋巴細(xì)胞“保護(hù)癌細(xì)胞”的能力。這一新發(fā)現(xiàn)為惡性腫瘤治療提供的傳統(tǒng)放化療法以外的副作用更小,、專一性更強(qiáng),、更有效的免疫“生物治療”奠定了堅(jiān)實(shí)的基礎(chǔ)。”
T淋巴細(xì)胞是一種免疫細(xì)胞,，在罹患惡性腫瘤時(shí),，它們中有的會(huì)發(fā)揮作用，奮力殺傷腫瘤細(xì)胞,，但是,，也有的T淋巴細(xì)胞非但不去殺傷腫瘤細(xì)胞，并且還會(huì)阻止其他淋巴細(xì)胞殺傷癌細(xì)胞,。因此,，如何調(diào)動(dòng)“良性”殺傷性T淋巴細(xì)胞勇猛殺“癌”的積極性，并有效抑制“惡性”調(diào)節(jié)性T淋巴細(xì)胞的破壞作用,，一直是國(guó)內(nèi)外醫(yī)學(xué)界科學(xué)家希望探索的“奧秘”,。
儲(chǔ)以微教授課題組經(jīng)研究發(fā)現(xiàn)，“BLP” 細(xì)菌脂蛋白與存在于T淋巴細(xì)胞表面的TLR-2受體“一對(duì)一配接”后,，會(huì)在兩群T淋巴細(xì)胞中誘導(dǎo)兩條不同的信號(hào),。對(duì)“良性”的殺傷性T淋巴細(xì)胞來說，激發(fā)了正向的信號(hào)通路,，而對(duì)“惡性”的調(diào)節(jié)性T淋巴細(xì)胞來說,，則激發(fā)了負(fù)向信號(hào)通路,，最終導(dǎo)致不同的效應(yīng)。相關(guān)深層次機(jī)制研究正在進(jìn)行中,。
上述成果已發(fā)表在最新一期的免疫學(xué)專業(yè)權(quán)威雜志 Journal of Immunology 上,，并被美國(guó)哈佛大學(xué)和英國(guó)劍橋大學(xué)等頂尖專家組成的國(guó)際權(quán)威機(jī)構(gòu)的在線科研評(píng)價(jià)系統(tǒng)“Faculty of 1000” 推薦為“必讀成果”。Faculty of 1000對(duì)該研究給予高度評(píng)價(jià)：“這一有趣的研究表明,，‘BLP’ 細(xì)菌脂蛋白發(fā)揮抗腫瘤效應(yīng),，不是通過直接作用于固有免疫系統(tǒng)或抗原提呈細(xì)胞，而是通過抑制調(diào)節(jié)性T淋巴細(xì)胞功能,，進(jìn)而促進(jìn)殺傷性T淋巴細(xì)胞的活性,。該研究成果為轉(zhuǎn)化醫(yī)學(xué)及免疫‘生物治療’奠定了堅(jiān)實(shí)的基礎(chǔ)。”（生物谷Bioon.com）
生物谷推薦原文出處：
The Journal of Immunology doi: 10.4049/jimmunol.1002320
TLR1/TLR2 Agonist Induces Tumor Regression by Reciprocal Modulation of Effector and Regulatory T Cells
Yi Zhang*,1, Feifei Luo*,1, Yuchan Cai*, Nan Liu*, Luman Wang*, Damo Xu? and Yiwei Chu*
Abstract
Using TLR agonists in cancer treatment can have either beneficial or detrimental effects. Therefore, it is important to determine their effect on the tumor growth and understand the underlying mechanisms in animal tumor models. In this study, we report a general immunotherapeutic activity of a synthetic bacterial lipoprotein (BLP), a TLR1/TLR2 agonist, on established lung carcinoma, leukemia, and melanoma in mice. Systemic treatment of 3LL tumor-bearing mice with BLP, but not LPS, led to a dose-dependent tumor regression and a long-lasting protective response against tumor rechallenge. The BLP-mediated tumor remission was neither mediated by a direct tumoricidal activity nor by innate immune cells, because it lacked therapeutic effect in immunodeficient SCID mice. Instead, BLP treatment reduced the suppressive function of Foxp3+ regulatory T cells (Tregs) and enhanced the cytotoxicity of tumor-specific CTL in vitro and in vivo. Furthermore, adoptive cotransfer of BLP-pretreated but not untreated CTL and Tregs from wild-type but not from TLR2?/? mice was sufficient to restore antitumor immunity in SCID mice by reciprocally modulating Treg and CTL function. These results demonstrate that the TLR1/TLR2 agonist BLP may have a general tumor therapeutic property involving reciprocal downregulation of Treg and upregulation of CTL function. This property may play an important role in the development of novel antitumor strategies.
