生物谷报道：根据圣弗兰西斯科，加利福尼亚大学神经外科助理教授，医学和理学博士Andrew T. Parsa领导的一项新研究：肿瘤免疫抵抗也许部分原因是由于丢失公认的肿瘤抑制基因所导致。这项发现今天发表在12月10日在线电子版上，并且也已经预定在《Nature Medicine》的一月分期刊上。
众所周知肿瘤细胞拥有许多方式去逃避免疫系统，其中包括隐藏在细胞表面的蛋白或者制造对免疫反应行为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肿瘤的演进的发展。在过去的四年中，Parsa和他的实验室把重点放在弄清楚高度神经胶质瘤相关的免疫抵抗与特定的突变的关系。恶性胶质瘤是头部肿瘤的最致命的一种之一，目前尚无特别有效的治疗手段。
研究人员筛选不同的突变细胞系，试着把把这些突变与抑制免疫系统的蛋白联系起来。
并发明了一种模型，它可以取出正常人的星形胶质细胞，然后使它们变成具有和恶性胶质瘤细胞一样行为的细胞。通过此模型的研究发现，在丧失PTEN功能的神经胶质瘤患者中，肿瘤细胞高表达B7-H1，这是有助于免疫抵抗的一种蛋白质。根据Parsa的研究：肿瘤细胞中高表达B7-H1被认为是肿瘤的防护屏障，并且在肿瘤细胞中B7-H1阳性的，与之联系的T细胞往往是不足的。他解释说：许多遗传突变能导致头部肿瘤的发生。但是特定类型的突变与PTEN功能的丧失和B7-H1的表达—免疫系统就很难杀死肿瘤。
Parsa的研究成果所暗示的意义超过了脑肿瘤的范围。在许多类型的肿瘤中都发现了PTEN功能的丢失，其中包括前列腺癌和乳腺癌。现实的治疗依赖免疫系统抗击肿瘤的方法或多或少的基于PTEN的功能。
原文出处：
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.
