CCR8在卵巢癌浸润性Treg上的表达与意义OA北大核心CSTPCD
Expression and significance of CCR8 on tumor-infiltrating Treg cells in ovarian cancer
目的:分析趋化因子受体8(C-C motif chemokine receptor 8,CCR8)在卵巢癌肿瘤浸润性调节性T细胞(regulatory T cell,Treg)中的表达,探讨CCR8对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上免疫检查点相关蛋白程序性细胞死亡蛋白1(programmed cell death protein 1,PD-1)、细胞素性T淋巴细胞抗原4(cytotoxic T-lymphocyte antigen 4,CTLA-4)、可诱导的T细胞共刺激分子(inducible T cell costimulators,ICOS)、淋巴细胞激活基因 3(lymphocyte activation gene 3,LAG-3)的表达;流式细胞术检测 CCR8变构抑制剂AZ084加入前后对C57BU6小鼠脾脏中初始CD4+T细胞向Treg分化的影响.结果:卵巢癌荷瘤小鼠肿瘤中Treg上的CCR8表达相比脾脏、外周血的Treg显著增高;相比CCR8-Treg,CCR8+Treg上免疫检查点相关蛋白表达更高;AZ084有效抑制小鼠脾脏中初始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.靶向消除CCR8+Treg可为改善卵巢癌肿瘤微环境的免疫抑制状态提供新思路.
Objective:To analyze the expression of C-C motif chemokine receptor 8(CCR8)in tumor-infiltrating regulatory T(Treg)cells in ovarian cancer and to investigate the role of CCR8 in Treg cell differentiation.Methods:An ID8 ovarian cancer cell-bearing model was established in C57BL/6 mice.The flow cytometry was used to detect the expression proportion of CCR8 on Treg in mouse tumor tissues,spleens and peripheral blood,and the expression levels of programmed cell death protein 1(PD-1),cytotoxic T-lymphocyte antigen 4(CTLA-4),inducible T-cell costimulator(ICOS)and lymphocyte-activation gene 3(LAG-3)on CCR8+Treg cells.The flow cytometry was also used to detect the changes in the differentiation ratio of naive CD4+T cells to Treg cells in the spleens of C57BL/6 mice before and after the addition of the CCR8 conformational inhibitor AZ084.Results:The expression of CCR8 on Treg cells in the tumors of ovarian cancer-bearing mice was significantly higher,compared with that in the spleens and peripheral blood.Compared with CCR8-Treg cells,CCR8+Treg cells also had a higher expression of immune checkpoint related proteins.AZ084 effectively inhibited the differentiation of naive CD4+T cells into Treg cells in the mouse spleens.Conclusion:CCR8+Treg cells constitute the major proportion of tumor-infiltrating Treg cells,and CCR8 acts as a primary marker of ovarian cancer-infiltrating Treg cells.Conformational modulation of the CCR8 protein can inhibit the differentiation ratio of Treg cells.The targeted elimination of CCR8+Treg cells may provide new insights for improving the immunosuppressive state of tumor microenvironment in ovarian cancer.
陶子琦;茅晔鹏;刘书娜;娄鉴芳;付鑫;张磊;严丽娜;王婷;王芳
南京医科大学第一附属医院检验学部,江苏 南京 210029||南京医科大学第一附属医院国家医学检验临床医学研究中心分中心,江苏 南京 210029南京医科大学第一附属医院检验学部,江苏 南京 210029||南京医科大学第一附属医院国家医学检验临床医学研究中心分中心,江苏 南京 210029||南京市妇幼保健院妇科,江苏 南京 210004
临床医学
卵巢癌趋化因子受体8调节性T细胞趋化因子
ovarian cancerC-C motif chemokine receptor 8regulatory T cellchemokine
《南京医科大学学报（自然科学版）》 2024 (003)
305-312 / 8
国家自然科学基金(82273199);江苏省自然科学基金(BK20221417)
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