High Levels of Class I Major Histocompatibility Complex mRNA Are Present in Epstein-Barr Virus-Associated Gastric Adenocarcinomas

High Levels of Class I Major Histocompatibility Complex mRNA Are Present in Epstein-Barr Virus-Associated Gastric Adenocarcinomas
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DOI:
10.3390/cells9020499
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发表时间:
2020-02-01
期刊:
影响因子:
6
通讯作者:
Mymryk, Joe S.
Mymryk, Joe S.
中科院分区:
生物学2区
文献类型:
--
作者:
Ghasemi, Farhad;Gameiro, Steven F.;Mymryk, Joe S.

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EB病毒(EBV)是造成大约9%的胃腺癌的原因。据报道,EBV编码的microRNA降低了I类主要组织相容性复合体(MHC-I)抗原呈递装置的功能,这可能使感染的细胞逃避适应性免疫反应。使用来自近400例人胃癌(GC)的数据,我们评估了EBV对MHC-I重链和轻链mRNA水平以及抗原加工和呈递所必需的多种其他组分的影响。出乎意料的是,与正常对照组织或其他GC亚型相比,这些基因的mRNA水平在EBV相关胃癌(EBVaGC)中同样高或更高。这种协同上调可能是EBVaGC中较高的肿瘤内干扰素γ水平的结果,这与T和自然杀伤(NK)细胞浸润增加的特征相关。这些结果表明,EBV编码的产物不能有效地降低人GC中MHC-I抗原呈递装置的mRNA水平。
Epstein-Barr virus (EBV) is responsible for approximately 9% of stomach adenocarcinomas. EBV-encoded microRNAs have been reported as reducing the function of the class I major histocompatibility complex (MHC-I) antigen presentation apparatus, which could allow infected cells to evade adaptive immune responses. Using data from nearly 400 human gastric carcinomas (GCs), we assessed the impact of EBV on MHC-I heavy and light chain mRNA levels, as well as multiple other components essential for antigen processing and presentation. Unexpectedly, mRNA levels of these genes were as high, or higher, in EBV-associated gastric carcinomas (EBVaGCs) compared to normal control tissues or other GC subtypes. This coordinated upregulation could have been a consequence of the higher intratumoral levels of interferon gamma in EBVaGCs, which correlated with signatures of increased infiltration by T and natural killer (NK) cells. These results indicate that EBV-encoded products do not effectively reduce mRNA levels of the MHC-I antigen presentation apparatus in human GCs.