在一項(xiàng)調(diào)查癌癥內(nèi)免疫反應(yīng)的研究中,來自佛羅里達(dá)州墨菲特癌癥中心及南佛羅里達(dá)大學(xué)的研究人員發(fā)現(xiàn),免疫系統(tǒng)抗原特異性CD4+ T細(xì)胞和髓系衍生抑制細(xì)胞（Myeloid derived suppressor cell,MDSC,在癌癥相關(guān)的免疫抑制中發(fā)揮重要作用的一種細(xì)胞)的相互作用顯著地改變了MDSC介導(dǎo)的抑制作用的性質(zhì).相反,在MDSCs與免疫系統(tǒng)CD8+ T細(xì)胞相互作用時(shí)并沒有觀察到這樣的作用.
這項(xiàng)研究發(fā)表于新一期的《癌癥研究》（Cancer Research）上,，這個(gè)期刊由美國癌癥研究協(xié)會(huì)出版。
據(jù)作者介紹,，已經(jīng)證實(shí)癌癥中免疫反應(yīng)不足是腫瘤逃逸的關(guān)鍵因素,，并且髓系衍生抑制細(xì)胞（MDSCs，正常情況下抑制免疫系統(tǒng),，防止免疫系統(tǒng)攻擊其它健康組織）能抑制抗腫瘤反應(yīng)并在腫瘤相關(guān)的免疫異常中發(fā)揮著重要的作用,。
此外,，研究表明，MDSCs阻斷了其它免疫系統(tǒng)細(xì)胞（如CD8+"殺手"T細(xì)胞）與不健康癌細(xì)胞表面外源抗原的結(jié)合（這樣做可以對(duì)不健康癌細(xì)胞進(jìn)行靶向標(biāo)記）,。"為了更好的了解癌癥中免疫缺陷的生物學(xué),，我們對(duì)MDSCs抗原特異性的性質(zhì)及它們引起抗原特異CD4+T細(xì)胞耐受的能力進(jìn)行了研究,，"通訊作者醫(yī)學(xué)博士Dmitry Gabrilovich說。"我們發(fā)現(xiàn)抗原特異CD4+T細(xì)胞能夠?qū)DSC轉(zhuǎn)變成強(qiáng)大的非特異抑制,，從而顯著地加強(qiáng)MDSC的免疫抑制作用,。但是，讓我們驚訝的是,，我們?cè)贑D8+T細(xì)胞中沒有看到相同的反應(yīng),。"
研究人員初步調(diào)查了在小鼠中建模的幾種腫瘤，但側(cè)重于2種特別感興趣的模型,。他們報(bào)告稱,，當(dāng)主要組織相容性復(fù)合體II分子（MHC II，只存在于少數(shù)專門化的細(xì)胞類型上）和MDSC通過細(xì)胞與細(xì)胞的接觸而進(jìn)行聯(lián)系時(shí),，MHC II在MDSC介導(dǎo)抑制作用的轉(zhuǎn)換中發(fā)揮了作用,。然而，這種作用依賴于MHC II的表達(dá),。
"這項(xiàng)研究首次表明,，激活的抗原特異性T細(xì)胞能夠通過將MDSC轉(zhuǎn)換成非特異抑制來增強(qiáng)MDSC的免疫抑制作用，從而限制了機(jī)體裝備強(qiáng)大免疫反應(yīng)的能力,，"作者總結(jié)道,。
研究人員建議，他們的研究可能揭示了一種機(jī)制,，可能作為一個(gè)"負(fù)反饋回路"旨在控制免疫反應(yīng)在癌癥中成為"失調(diào)",。
該消息由H.Lee莫菲特癌癥中心及研究所提供。（生物谷bioon.com）
doi:10.1158/1538-7445.AM2011-3648
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S100A9 play a role in MDSC expansion and migration but not in their activation
homas Condamine, Pingyan Cheng, Je-In Youn, Myrna L. Ortiz, Thomas Vogl, Johannes Roth, and Dmitry I. Gabrilovich
Abstract： S100A9 is a pro-inflammatory molecule, secreted by myeloid cells, which has been reported to recruit leukocytes to the sites of inflammation or tumors. Up-regulation of S100A9 expression in myeloid progenitor cells was implicated in inhibition of DC differentiation and promotion of expansion of myeloid-derived suppressor cells (MDSC). These cells have been well described as a major component used by the tumor to be protected from the immune system. In order to determine if extracellular and intracellular S100A9 has similar effects on myeloid cell differentiation and function, we evaluated the effect of recombinant S100A9. Our results demonstrated that in contrast to overexpression of S100A9 in hematopoietic progenitor cell (HPC), the treatment of HPC with recombinant S100A9 did not affect their differentiation to mature macrophages, or dendritic cells. The same treatment does not affect the suppressive activity of MDSC purified from naïve or tumor-bearing mice either. However, recombinant S100A9 had strong chemotactic effect on MDSC. Interestingly, its effect on immature myeloid cells isolated from naïve tumor-free mice was substantially lower. Recently, it has been suggested that MDSC need two different signals: one – required for their expansion and inhibited differentiation of mature myeloid cells and the other one – for activation. Our data suggest that S100A9 may mediate first signals but not the second one. Intracellular up-regulation of S100A9 promotes expansion of MDSC and contributes to block of their differentiation, whereas extracellular S100A9 via cell receptors induce MDSC migration. A better understanding of how MDSC migrate into the tumor and how S100A9 is involved in this process could lead to the generation of new treatment aiming to block the migration of MDSC inside the tumor.
