<em>MiR-155</em> driven loss of ICOSL and SOCS1 in EBV+ gastric cancers renders \ abundant cytotoxic T cells ineffective, enabling immune evasion
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Poorly differentiated gastric carcinomas (PDGC) can be further subdivided into Epstein-Barr virus (EBV) positive (+) and EBV-negative (-) subtypes. EBV infection induces miR-155 expression. miR-155 targets ICOSL, a critical immune checkpoint. This study was done to compare the EBV+ and EBV- gastric cancers for their mechanisms of tumor rejection and how EBV-induced oncogenic miR-155 controls these events. For this, we interrogated PDGC samples for EBV status (by staining for EBV encoded factors), paralleled by CD8, PDL1, PD1, ICOSL, ICOS, MHC-I, SOCS1, and miR-155. We found that, despite the similar histological patterns of the PDGC cancer cells, EBV-driven induction of miR-155 suppresses SOCS1 expression, resulting in intense cytotoxic T-cell infiltration, but also loss of the other miR-155 target, ICOSL, making tumor cells invisible to the surrounding intense T cell infiltration. Conversely, EBV-negative tumors retain ICOSL/SOCS1 expression, but exhibit minimal T-cell infiltration, p..., All work was done using immunohistochemistry (for all proteins studied) and in-situ hybridization (for EBV-encoded small RNAs (EBER-1/2) and miR-155) of mostly tumor tissue arrays. all the work was done based on the methods described in very detail in 1- G. J. Nuovo. A methodology for the combined in situ analyses of the precursor and mature forms of microRNAs and correlation with their putative targets. Nat. Protoc. 4:107â115 (2009). 2- G. J. Nuovo. In Situ Molecular Pathology and Co-Expression Analyses (Second Edition). Book. Academic Press, ISBN 9780128206539 (2020). , # *MiR-155* driven loss of ICOSL and SOCS1 in EBV+ gastric cancers renders \ abundant cytotoxic T cells ineffective, enabling immune evasion Dataset DOI: [10.5061/dryad.gf1vhhn3q](https://doi.org/10.5061/dryad.gf1vhhn3q) ## Description of the data and file structure these are images of different samples of tumors stained with a panel of different immune and oncogenic markers ### Files and variables #### File: FIG._1_A_H_E.jpg **Description:** Fig 1A, is the H&E-stained image of an EBV-positive gastric cancer. #### File: FIG._1_B_H_E.jpg **Description:** Magnification (high resolution of the HE stained EBV-positive gastric cancer from Fig. 1A) #### File: FIG._1_C_miR155.jpg **Description:** miR-155 has been previously reported to be induced by EBV infection. This figure shows that EBV+ gastric cancers are as expected miR-155 positive. The tumor was analyzed by in-situ hybridization for miR-155. The signal for mir-155 positive is dark blue. #### File: FIG._1_D_EBER_12.jpg **..., ,
低分化胃癌（Poorly differentiated gastric carcinomas, PDGC）可进一步分为EB病毒（Epstein-Barr virus, EBV）阳性亚型与EB病毒阴性亚型。EB病毒感染可诱导miR-155的表达，而miR-155的靶标为ICOSL——一种关键的免疫检查点分子。本研究旨在对比EB病毒阳性与阴性胃癌的肿瘤排斥机制，以及EB病毒诱导的致癌性miR-155如何调控这些过程。 为此，我们通过染色检测EB病毒编码因子的方式来确定低分化胃癌样本的EB病毒感染状态，同时同步检测CD8、PDL1、PD1、ICOSL、ICOS、MHC-I、SOCS1的表达水平以及miR-155的表达量。研究发现，尽管两类低分化胃癌的癌细胞组织学模式相似，但EB病毒驱动的miR-155表达上调会抑制SOCS1的表达，这不仅会引发强烈的细胞毒性T细胞浸润，同时还会导致另一miR-155靶标ICOSL的表达缺失，使得肿瘤细胞能够逃脱周围密集的T细胞浸润的杀伤作用。与之相反，EB病毒阴性的肿瘤则保留了ICOSL与SOCS1的表达，但仅存在极少量的T细胞浸润，…… 所有实验均通过免疫组化（immunohistochemistry）（针对所有检测的蛋白）和原位杂交（in-situ hybridization）（针对EB病毒编码小RNA EBER-1/2以及miR-155）完成，实验样本主要为肿瘤组织芯片。 所有实验均基于两篇详细阐述的方法开展： 1. G. J. Nuovo. 《microRNA前体与成熟体联合原位分析方法及其与推定靶标的相关性研究》. *Nature Protocols*, 4:107–115 (2009). 2. G. J. Nuovo. 《原位分子病理学与共表达分析（第二版）》. 学术出版社, ISBN 9780128206539 (2020). # *miR-155*驱动的EB病毒阳性胃癌中ICOSL与SOCS1的缺失使得大量细胞毒性T细胞无法发挥杀伤功能，进而促成免疫逃逸 数据集DOI：[10.5061/dryad.gf1vhhn3q](https://doi.org/10.5061/dryad.gf1vhhn3q) ## 数据与文件结构说明 本数据集包含不同肿瘤样本经多种免疫及致癌标志物染色后的图像。 ### 文件与变量 #### 文件：FIG._1_A_H_E.jpg **描述：** 图1A为EB病毒阳性胃癌的苏木精-伊红（Hematoxylin-Eosin, H&E）染色图像。 #### 文件：FIG._1_B_H_E.jpg **描述：** 该图像为图1A中EB病毒阳性胃癌HE染色样本的高倍放大视图。 #### 文件：FIG._1_C_miR155.jpg **描述：** 既往研究表明EB病毒感染可诱导miR-155的表达。本图证实EB病毒阳性胃癌确实呈miR-155阳性。我们通过原位杂交技术对样本中的miR-155进行了检测，miR-155阳性信号呈深蓝色。 #### 文件：FIG._1_D_EBER_12.jpg **描述：** ……，
