RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
EBV 相关胃癌中的肿瘤浸润 T 细胞表现出高水平的多种活化标志物、效应基因表达和耗竭
英文原题：Tumor-Infiltrating T Cells in EBV-Associated Gastric Carcinomas Exhibit High Levels of Multiple Markers of Activation, Effector Gene Expression, and Exhaustion.
查看英文原题
Tumor-Infiltrating T Cells in EBV-Associated Gastric Carcinomas Exhibit High Levels of Multiple Markers of Activation, Effector Gene Expression, and Exhaustion.
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中文摘要
EB病毒（EBV）是一种γ疱疹病毒，与约10%的胃癌（GC）和1.5%的人类癌症相关。EBV相关胃癌（EBVaGC）在病理和临床特征上均不同于EBV阴性胃癌（EBVnGC），表现出不同的分子病理特征、治疗反应和患者预后。
然而，EBVaGC的肿瘤免疫图谱尚未得到充分研究。本研究系统、全面地分析了EBVaGC和EBVnGC的基因表达及免疫图谱特征。与EBVnGC相比，EBVaGC呈现多种T细胞炎症表型特征，包括更多T细胞和NK细胞浸润、免疫检查点标志物（BTLA、CD96、CTLA4、LAG3、PD1、TIGIT和TIM3）表达增加，以及多种T细胞效应分子表达升高。EBVaGC中抗肿瘤免疫相关因子（PDL1、CD155、CEACAM1、半乳糖凝集素-9和IDO1）的表达也更高。六种EBV编码的miRNA（miR-BARTs 8-3p、9-5p、10-3p、22、5-5p和14-3p）与免疫检查点受体及多种抗肿瘤免疫标志物的表达呈显著负相关。EBVaGC与EBVnGC在肿瘤免疫图谱上的这些显著差异，可能有助于解释两者病理和临床结局的部分差异；EBV阳性状态也可能成为胃癌免疫治疗应用的潜在生物标志物。
展开英文摘要原文
Epstein-Barr virus (EBV) is a gamma-herpesvirus associated with 10% of all gastric cancers (GCs) and 1. 5% of all human cancers. EBV-associated GCs (EBVaGCs) are pathologically and clinically distinct entities from EBV-negative GCs (EBVnGCs), with EBVaGCs exhibiting differential molecular pathology, treatment response, and patient prognosis.
However, the tumor immune landscape of EBVaGC has not been well explored. In this study, a systemic and comprehensive analysis of gene expression and immune landscape features was performed for both EBVaGC and EBVnGC. EBVaGCs exhibited many aspects of a T cell-inflamed phenotype, with greater T and NK cell infiltration, increased expression of immune checkpoint markers (BTLA, CD96, CTLA4, LAG3, PD1, TIGIT, and TIM3), and multiple T cell effector molecules in comparison with EBVnGCs. EBVaGCs also displayed a higher expression of anti-tumor immunity factors (PDL1, CD155, CEACAM1, galectin-9, and IDO1).
Six EBV-encoded miRNAs (miR-BARTs 8-3p, 9-5p, 10-3p, 22, 5-5p, and 14-3p) were strongly negatively correlated with the expression of immune checkpoint receptors and multiple markers of anti-tumor immunity. These profound differences in the tumor immune landscape between EBVaGCs and EBVnGCs may help explain some of the observed differences in pathological and clinical outcomes, with an EBV-positive status possibly being a potential biomarker for the application of immunotherapy in GC.
论文信息
- 作者
- Salnikov M、Prusinkiewicz MA、Lin S、Ghasemi F、Cecchini MJ、Mymryk JS
- 单位
- Department of Microbiology and Immunology, Western University, London, ON N6A 3K7, Canada.United Kingdom
- 文献类型
- 非美国政府资助研究
- 期刊
- Viruses2023 Jan 7
- 原文标识
- PubMed 36680216 · DOI 10.3390/v15010176
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