Objective: To investigate the immunotherapeutic roles and functions of C-C Motif Chemokine Receptor 8 (CCR8) molecule in gastric cancer (GC). Materials and Methods: Clinicopathological features of 95 GC cases were collected by a follow-up survey. The expression level of CCR8 was measured by immunohistochemistry (IHC) staining and analyzed with the cancer genome atlas database. The relationship between CCR8 expression and Clinicopathological features of GC cases was evaluated by univariate and multivariate analysis. Flow cytometry was used to determine the expression of cytokines and the proliferation of CD4+ regulator T cells (Tregs) and CD8+ T cells. Results: An upregulated expression of CCR8 in GC tissues was associated with tumor grade, nodal metastasis, and overall survival (OS). Tumor-infiltrated Tregs with higher expression of CCR8 produced more IL10 molecules in vitro. In addition, anti-CCR8 blocking downregulated IL10 expression produced by CD4+ Tregs, and reversed the suppression by Tregs on the secretion and proliferation of CD8+ T cells. Conclusion: CCR8 molecule could be a prognostic biomarker for GC cases and a therapeutic target for immune treatments.

中文翻译：

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一种新型胃癌预后生物标志物 CCR8 和抗 CCR8 阻断可减弱体外 Tregs 的免疫抑制能力。

目的：探讨CC基序趋化因子受体8（CCR8）分子在胃癌（GC）中的免疫治疗作用和功能。材料与方法：通过随访调查收集95例GC病例的临床病理特征。通过免疫组织化学 (IHC) 染色测量 CCR8 的表达水平，并使用癌症基因组图谱数据库进行分析。通过单变量和多变量分析评估CCR8表达与GC病例临床病理特征之间的关系。采用流式细胞术测定细胞因子的表达以及CD4+调节性T细胞(Treg)和CD8+T细胞的增殖情况。结果：GC 组织中 CCR8 表达上调与肿瘤分级、淋巴结转移和总生存期 (OS) 相关。CCR8 表达较高的肿瘤浸润性 Tregs 在体外产生更多的 IL10 分子。此外，抗CCR8阻断下调CD4+Tregs产生的IL10表达，并逆转Tregs对CD8+T细胞的分泌和增殖的抑制。结论：CCR8分子可以作为GC病例的预后生物标志物和免疫治疗的治疗靶点。