2009年2月27日星期五

Nature Immunology:肿瘤可能通过特殊机制逃避免疫


健康的细胞会表达出一种小RNA,帮助它们回避来自免疫系统不必要的识别和进攻。在8月出版的《自然—免疫学》期刊上,研究人员对这一机制进行了解释,并推测肿瘤可能也利用了同样的机制来逃逸检测。
在遇到病毒感染等压力状况时,两种蛋白质MICA和MICB会被免疫细胞上表达的受体NKG2D所识别。对这些由压力诱导的蛋白质的探测会触发一种可去除压力源的免疫反应。而病毒则会使用一种名为小RNA的短链RNA来抑制MICA和MICB的表达,从而逃避相应的免疫反应。
以色列希伯来大学Ofer Mandelboim和同事指出,类似于这种病毒,健康的非压力型人类细胞也能表达出抑制MICA和MICB表达的小RNA,因此,健康细胞能逃避免疫系统的探测。与健康组织相比,人类的许多肿瘤组织也表达出过量的这类小RNA,从而让它们逃过免疫系统的识别,这就是问题的严重性所在。 (生物谷Bioon.com)
生物谷推荐原始出处:
Nature Immunology,doi:10.1038/ni.1642,Noam Stern-Ginossar,Ofer Mandelboim
Human microRNAs regulate stress-induced immune responses mediated by the receptor NKG2D
Noam Stern-Ginossar1, Chamutal Gur1, Moshe Biton1, Elad Horwitz1, Moran Elboim1, Noa Stanietsky1, Michal Mandelboim2 & Ofer Mandelboim1
Abstract
MICA and MICB are stress-induced ligands recognized by the activating receptor NKG2D. A microRNA encoded by human cytomegalovirus downregulates MICB expression by targeting a specific site in the MICB 3' untranslated region. As this site is conserved among different MICB alleles and a similar site exists in the MICA 3' untranslated region, we speculated that these sites are targeted by cellular microRNAs. Here we identified microRNAs that bound to these MICA and MICB 3' untranslated region sequences and obtained data suggesting that these microRNAs maintain expression of MICA and MICB protein under a certain threshold and facilitate acute upregulation of MICA and MICB during cellular stress. These microRNAs were overexpressed in various tumors and we demonstrate here that they aided tumor avoidance of immune recognition.
1 Lautenberg Center for General and Tumor Immunology, The Hebrew University, The BioMedical Research Institute, Hadassah Medical School, Jerusalem 91120, Israel.2 Clinical Virology Unit, Tel-Hashomer, Ramat Gan 52621, Israel.

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