Salnikov Mikhail Y, Fonseca Gregory J, Mymryk Joe S
Department of Microbiology and Immunology, Western University, London, ON N6A 3K7, Canada.
Meakins-Christie Laboratories, Research Institute of the McGill University Health Centre, Montreal, QC H4A 3J1, Canada.
Cancers (Basel). 2023 Jun 14;15(12):3178. doi: 10.3390/cancers15123178.
Epstein-Barr virus (EBV) is a gamma-herpesvirus associated with nearly 10% of gastric cancers (GCs). These EBV-associated GCs (EBVaGCs) are molecularly, histopathologically, and clinically distinct from EBV-negative GCs (EBVnGCs). While viral genes in EBVaGCs contribute to the carcinogenesis process, viral proteins also represent foreign antigens that could trigger enhanced immune responses compared to EBVnGCs. Despite prior investigations of the EBVaGC tumor microenvironment (TME), the cellular composition has not been thoroughly explored. In this study, cellular subpopulations overrepresented in EBVaGCs were identified and molecularly characterized. Genes consistently expressed across both bulk tumor and single-cell RNA sequencing data were highlighted, with the expression across the identified cellular subpopulations analyzed. As expected, based on existing histopathological analysis, EBVaGC is characterized by abundant lymphocytic infiltration of the stroma. Our molecular analysis identified three unique immune cell subpopulations in EBVaGC: T and B cells expressing high levels of proliferation markers and B cells expressing T cell features. The proliferating T cell cluster also expressed markers of follicular T helper cells. Overall, EBVaGC also exhibited unique features indicative of a higher inflammatory response. These substantial differences within the TME suggest that further detailed exploration of the cellular composition of EBVaGCs is needed, which may identify cellular subpopulations and phenotypes associated with patient outcomes.
爱泼斯坦-巴尔病毒(EBV)是一种γ-疱疹病毒,与近10%的胃癌(GC)相关。这些与EBV相关的胃癌(EBVaGC)在分子、组织病理学和临床上与EBV阴性胃癌(EBVnGC)不同。虽然EBVaGC中的病毒基因有助于致癌过程,但病毒蛋白也代表外来抗原,与EBVnGC相比,可能引发更强的免疫反应。尽管之前对EBVaGC肿瘤微环境(TME)进行了研究,但细胞组成尚未得到充分探索。在本研究中,确定了在EBVaGC中过度表达的细胞亚群并对其进行了分子表征。强调了在批量肿瘤和单细胞RNA测序数据中一致表达的基因,并分析了在所确定的细胞亚群中的表达情况。正如预期的那样,基于现有的组织病理学分析,EBVaGC的特征是基质中有大量淋巴细胞浸润。我们的分子分析在EBVaGC中确定了三个独特的免疫细胞亚群:表达高水平增殖标志物的T细胞和B细胞以及表达T细胞特征的B细胞。增殖的T细胞簇还表达滤泡辅助性T细胞标志物。总体而言,EBVaGC还表现出表明更高炎症反应的独特特征。TME内的这些实质性差异表明,需要对EBVaGC的细胞组成进行进一步详细探索,这可能会确定与患者预后相关的细胞亚群和表型。
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