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.
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TAO Ziqi, MAO Yepeng, LIU Shu’na, LOU Jianfang, FU Xin, ZHANG Lei, YAN Li’na, WANG Ting, WANG Fang. Expression and significance of CCR8 on tumor⁃infiltrating Treg cells in ovarian cancer[J].,2024,(3):305-312.