生物谷報(bào)道：根據(jù)圣弗蘭西斯科，加利福尼亞大學(xué)神經(jīng)外科助理教授，醫(yī)學(xué)和理學(xué)博士Andrew T. Parsa領(lǐng)導(dǎo)的一項(xiàng)新研究：腫瘤免疫抵抗也許部分原因是由于丟失公認(rèn)的腫瘤抑制基因所導(dǎo)致,。這項(xiàng)發(fā)現(xiàn)今天發(fā)表在12月10日在線電子版上,，并且也已經(jīng)預(yù)定在《Nature Medicine》的一月分期刊上,。
眾所周知腫瘤細(xì)胞擁有許多方式去逃避免疫系統(tǒng),，其中包括隱藏在細(xì)胞表面的蛋白或者制造對(duì)免疫反應(yīng)行為抑制的蛋白等普遍的策略。一些研究者相信免疫抵抗有助于腫瘤的演進(jìn)的發(fā)展,。在過去的四年中,，Parsa和他的實(shí)驗(yàn)室把重點(diǎn)放在弄清楚高度神經(jīng)膠質(zhì)瘤相關(guān)的免疫抵抗與特定的突變的關(guān)系。惡性膠質(zhì)瘤是頭部腫瘤的最致命的一種之一,，目前尚無特別有效的治療手段,。
研究人員篩選不同的突變細(xì)胞系，試著把把這些突變與抑制免疫系統(tǒng)的蛋白聯(lián)系起來,。
并發(fā)明了一種模型，它可以取出正常人的星形膠質(zhì)細(xì)胞,，然后使它們變成具有和惡性膠質(zhì)瘤細(xì)胞一樣行為的細(xì)胞,。通過此模型的研究發(fā)現(xiàn)，在喪失PTEN功能的神經(jīng)膠質(zhì)瘤患者中,，腫瘤細(xì)胞高表達(dá)B7-H1,，這是有助于免疫抵抗的一種蛋白質(zhì)。根據(jù)Parsa的研究：腫瘤細(xì)胞中高表達(dá)B7-H1被認(rèn)為是腫瘤的防護(hù)屏障,，并且在腫瘤細(xì)胞中B7-H1陽性的,，與之聯(lián)系的T細(xì)胞往往是不足的。他解釋說：許多遺傳突變能導(dǎo)致頭部腫瘤的發(fā)生,。但是特定類型的突變與PTEN功能的喪失和B7-H1的表達(dá)—免疫系統(tǒng)就很難殺死腫瘤,。
Parsa的研究成果所暗示的意義超過了腦腫瘤的范圍。在許多類型的腫瘤中都發(fā)現(xiàn)了PTEN功能的丟失,，其中包括前列腺癌和乳腺癌?，F(xiàn)實(shí)的治療依賴免疫系統(tǒng)抗擊腫瘤的方法或多或少的基于PTEN的功能。
原文出處：
http://www.eurekalert.org/pub_releases/2006-12/uoc--cil120806.php
Cancer immunoresistance linked to loss of tumor suppressor gene
Cancer immunoresistance may be partially due to loss of a well-known tumor suppressor gene, according to new research led by Andrew T. Parsa, MD, PhD, assistant professor of neurological surgery at the University of California, San Francisco.
The findings are reported today (December 10) online and are scheduled to appear in the January issue of Nature Medicine.
It has been known for a long time that cancer cells have many different ways to avoid the immune system, including the common strategies of hiding proteins that are normally expressed on the cell surface or making proteins that act to suppress immune responses, according to Parsa. Some researchers believe that immunoresistance may contribute to cancer progression and development, he added.
Over the past four years, Parsa抯 lab has focused on trying to understand how specific mutations associated with high grade glioma correlate with immunoresistance. Malignant glioma is among the deadliest types of brain cancer for which there currently is no effective treatment.
揗y colleague James Waldron and I began screening different cell lines for mutations and trying to match these mutations up with proteins that suppress the immune system,?Parsa said.
The researchers began to see an interesting trend. Glioma cells with mutation in a specific gene called the phosphatase and tensin homolog gene, or PTEN, seemed more resistant to the immune system than glioma cells with normal PTEN function. Determining the mechanism responsible for the immunoresistance proved more difficult.
揊ortunately, Russ Pieper抯 lab here at UCSF had developed a model that took normal human astrocytes and made them act like a malignant glioma. This allowed us to study the effects of PTEN mutation in a very well controlled manner,?Parsa said.
In glioma patients who have lost PTEN function, the tumor cells were found to express high levels of B7-H1, a protein that contributes to immunoresistance. According to Parsa, high levels of B7-H1 on a cancer cell can be thought of as a protective barrier, and T-cells that come in contact with B7-H1 positive cancer cells are ineffective.
