EBV相关的胃淋巴上皮瘤样癌（EBVaGLELC）是胃癌（GC）中数量较少的一种，对其肿瘤微环境（TME）和治疗策略的研究仍然缺乏。本研究旨在阐明这种罕见疾病的免疫特征，并进一步帮助发展更有效的治疗选择。我们在中国西部医院进行了2019年至2022年的回顾性分析，以揭示EBV阳性GLELC的免疫学特征。我们将指出胃腺癌（GAC）和EBVaGLELC之间的免疫细胞亚群和肿瘤血管结构的差异。共回顾研究了13例GELEC患者和8例GAC患者。随后通过多重免疫荧光染色（mIF）确认了免疫细胞谱的异质性，发现EBV相关的GLELC群中CD3+T细胞、CD8+T细胞和Treg细胞的比例较高。这种独特的肿瘤微环境可能为治疗提供优势，且这种罕见的GC亚型患者可能是免疫检查点抑制剂（ICIs）的良好候选人。EBV阳性的GLELC中的血管生成可能比胃腺癌（GAC）要轻度，这一特点可能降低它们对抗血管生成治疗的敏感性。此外，我们报道了一名52岁的男性晚期EBV阳性的GLELC患者，他对联合治疗显示出良好的反应。重复评估显示持续的部分缓解（PR），无进展生存期（PFS）至今已超过34个月。与GAC相比，EBVaGLELC显示出更高的T细胞浸润和较轻的血管生成。它呈现出相对“炽热”的肿瘤微环境，这可能为EBV相关的GLELC治疗提供合理性。© 2023 作者。癌症医学由John Wiley＆Sons Ltd出版。

Epstein-Barr virus (EBV)-associated gastric lymphoepithelioma-like carcinoma (EBVaGLELC) represents a small number of gastric cancer (GC), and research on tumor microenvironment (TME) and treatment strategy are still lacking.Here, we aim to elucidate the immune features of this rare disease and further help to develop more effective treatment options.A retrospective analysis was conducted between 2019 to 2022 in West China Hospital to reveal the immunological characteristics of EBV-positive GLELC. The difference of immune cell subset and tumor vascular structure between gastric denocarcinoma (GAC) and EBVaGLELC will be pointed out.13 patients with GELEC and 8 patients with GAC were retrospectively studied. The heterogeneity of the immune cell profile was then confirmed through multiplexed immunofluorescence staining (mIF), which revealed a higher proportion of CD3+ T cells, CD8+ T cells, and Treg cells in the EBV-associated GLELC group. Such a distinct TME may provide therapeutic advantages, and patients with this rare subtype of GC could be good candidates for immune checkpoint inhibitors (ICIs). Angiogenesis in EBV-positive GLELC may be less intense than that in gastric adenocarcinoma (GAC), a feature that might decrease their susceptibility to antiangiogenic therapy. Furthermore, we reported a 52-year-old male with advanced EBV-positive GLELC who showed a favorable response to the combined therapy with . A repeat evaluation showed sustained partial response (PR), and the progression-free survival (PFS) was more than 34 months until now.Compared with GAC, EBVaGLELC revealed higher T cell infiltration and less intense of angiogenesis. It displays relatively "hot" TME that may provide the rationality to treat with immunotherapy in EBV-related GLELC.© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.