CCR8在卵巢癌浸润性Treg上的表达与意义
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南京医科大学第一附属医院检验学部

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国家自然科学基金项目(面上项目,重点项目,重大项目)


Expression and Significance of CCR8 on Tumor-Infiltrating Treg Cells in Ovarian Cancer
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    摘要:

    分析CCR8在卵巢癌肿瘤浸润性Treg中的表达,探讨CCR8对于Treg分化的作用。方法:构建C57BL/6小鼠卵巢癌细胞ID8荷瘤模型;流式细胞术检测小鼠肿瘤组织、脾脏和外周血中Treg上CCR8的表达比例,CCR8+Treg上PD-1、CTLA-4、ICOS、LAG-3的表达;流式细胞术检测CCR8变构抑制剂AZ084加入前后对于C57BL/6小鼠脾脏中Naive CD4+T细胞向Treg分化的比例的变化。结果:卵巢癌荷瘤小鼠的肿瘤中CCR8在Treg上的表达相较于脾脏、外周血中有显著增高;相较于CCR8-Treg, CCR8+Treg上免疫检查点表达也更高;AZ084有效抑制小鼠脾脏中Naive CD4+T细胞向Treg的分化。结论:CCR8+Treg在肿瘤浸润性Treg中占主要比例, CCR8作为卵巢癌浸润性Treg的主要标志物,变构CCR8蛋白可以抑制Treg的分化比例。提示靶向消除CCR8+Treg可以为改善卵巢癌微环境的免疫抑制状态提供新思路。

    Abstract:

    Objective: To investigate the expression profile of CCR8 in tumor-infiltrating Tregs within ovarian cancer and to elucidate its impact on Treg differentiation. Methods: C57BL/6 mouse model bearing ID8 ovarian cancer cells was established. Flow cytometry assays were conducted to measure the expression ratios of CCR8 on Tregs in mouse tumor tissues, spleen, and peripheral blood, as well as the expression of immune checkpoints PD-1, CTLA-4, ICOS, and LAG-3 on CCR8+Tregs. Results: The tumors in the ovarian cancer-bearing mice exhibited a marked increase in CCR8 expression on Tregs when compared to spleen and peripheral blood. Additionally, CCR8+ Tregs demonstrated elevated levels of immune checkpoint markers relative to CCR8-Tregs.The conformational inhibitor AZ084 was effective in suppressing the differentiation of Naive CD4+ T cells into Tregs in the mouse spleen. Conclusion: CCR8+ Tregs are predominant among tumor-infiltrating Tregs. CCR8 acts as a primary biomarker for Tregs infiltrating ovarian cancer, and conformational alteration of CCR8 protein can inhibit Treg differentiation. This suggests that targeting the depletion of CCR8+ Tregs may provide a new avenue for mitigating the immunosuppressive status within the ovarian cancer microenvironment.

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  • 收稿日期:2023-09-01
  • 最后修改日期:2023-12-05
  • 录用日期:2024-02-27
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