Tregs 是实体瘤免疫抑制的关键驱动因素。作为Tregs上重要的趋化因子受体，CCR8对肿瘤免疫的调节作用越来越受到关注。然而目前关于CCR8在卵巢癌免疫微环境中的研究尚不清楚。通过生物信息学分析比较卵巢肿瘤组织中外周循环和浸润的CD4 T细胞转录组差异。采用RT-PCR检测外周血及卵巢肿瘤组织中CD4+T细胞趋化因子受体相关差异基因的表达水平。采用多参数流式细胞术检测不同样本类型中CD4 CCR8 Tregs和CD4 CCR8- Tregs的比例和表型特征。在多个水平上检测CCR8配体的表达水平。目的 通过建立体外趋化系统，探讨CCR8-CCL1和CCR8-CCL18轴在CD4 CCR8 Tregs迁移和侵袭卵巢肿瘤组织中的重要作用。本研究发现外周循环CD4之间存在显着差异的基因表达谱。卵巢肿瘤组织中存在T细胞和浸润性CD4 T细胞，其中趋化因子-趋化因子受体信号通路中三组差异基因均显着富集。卵巢癌组织浸润性CD4 T细胞中CCR8的表达水平显着高于健康对照者和卵巢癌患者外周血中的表达水平，且CCR8的高表达与肿瘤分期晚期和分化差显着相关。 CD4 CCR8 Tregs是卵巢肿瘤组织中浸润性CD4 Tregs的主要类型，具有更强的免疫抑制表型、分泌更多的抑制性细胞因子、更强的增殖能力。 CCR8对应的配体CCL1和CCL18在卵巢肿瘤组织中显着过表达，并且CCR8-CCL1和CCR8-CCL18轴在CD4 CCR8 Tregs向卵巢肿瘤组织中的迁移和浸润中起关键作用。本研究结果可能有助于了解肿瘤中Tregs的表型特征和招募过程，为改善卵巢癌微环境的免疫抑制状态提供新思路。©2023。作者。

Tregs are key drivers of immunosuppression in solid tumors. As an important chemokine receptor on Tregs, the regulatory effect of CCR8 on tumor immunity has received more and more attention. However, the current research on CCR8 in the immune microenvironment of ovarian cancer has not been clear.Bioinformatics analysis was used to compare the transcriptome differences between CD4+ T cells in the peripheral circulation and infiltrated in ovarian tumor tissues. RT-PCR was used to detect the expression levels of chemokine receptor-related differential genes on CD4+ T cells in peripheral blood and ovarian tumor tissues. Multiparameter flow cytometry was used to detect the proportion and phenotypic characteristics of CD4+CCR8+ Tregs and CD4+CCR8- Tregs in different sample types. The expression level of CCR8 ligands was detected at multiple levels. To explore the important role of CCR8-CCL1 and CCR8-CCL18 axis in the migration and invasion of CD4+CCR8+ Tregs into ovarian tumor tissues by establishing a chemotaxis system in vitro.In this study, significantly different gene expression profiles were found between peripheral circulating CD4+ T cells and infiltrating CD4+ T cells in ovarian tumor tissues, in which chemokine-chemokine receptor signaling pathway was significantly enriched in all three groups of differential genes. The expression level of CCR8 in infiltrating CD4+ T cells of ovarian cancer tissue was significantly higher than that in peripheral blood of healthy controls and ovarian cancer patients, and high expression of CCR8 was significantly correlated with advanced tumor stage and poor differentiation. CD4+CCR8+ Tregs are the main type of infiltrating CD4+ Tregs in ovarian tumor tissues, which have stronger immunosuppressive phenotypes, secrete more inhibitory cytokines and have stronger proliferation ability. The ligands CCL1 and CCL18 corresponding to CCR8 were significantly overexpressed in ovarian tumor tissues, and the CCR8-CCL1 and CCR8-CCL18 axis played a key role in the migration and infiltration of CD4+CCR8+ Tregs into ovarian tumor tissues.The results of this study may help to understand the phenotypic characteristics and recruitment process of Tregs in the tumor, and provide new ideas for improving the immunosuppressive status of the ovarian cancer microenvironment.© 2023. The Author(s).