Down-Regulation of CD25 Expression on the Surface of Activated Tumor-Infiltrating Lymphocytes in Human Cervical Carcinoma

ABSTRACT: To investigate the activation status of tumor-infiltrating lymphocytes (TILs) within the tumor milieu of human cervical carcinoma, we quantitatively measured and compared the activation markers on lymphocyte subpopulations which infiltrating normal and neoplastic cervix. A total of 20 patients with stage IA to IIA cervical cancer (cancer group) and 10 women with normal cervix (control group) were enrolled in this study. Mononuclear cells were isolated from tissue specimens by mechanical dispersal technique and three-color flow cytometry was utilized for the quantification of activation markers on lymphocyte subsets. Compared with control group, lymphocytes isolated from cancer tissue consisted of higher proportions of B cells (7.23% ± 4.49% vs. 3.67% ± 3.19%, P = 0.016) and T cells (72.33% ± 8.70% vs. 53.15% ± 17.36%, P = 0.004), but an inverted CD4:CD8 ratio (0.74 ± 0.27 vs. 1.14 ± 0.28, P = 0.002) and decreased NK cells (7.53% ± 4.33% vs. 16.00% ± 11.82%, P = 0.035). Low expression of CD25, but not CD69 and HLA-DR was observed on both CD4⁺CD3⁺ and CD8⁺CD3⁺ T cells derived from cervical cancer (P < 0.0001). Further dual activation marker analysis demonstrated that the expression of CD25 was dissociated from CD69 and HLA-DR on the same TILs in cancer tissue (P < 0.001). TILs in the tumor microenvironment can be functionally inhibited and lose the ability of clonal proliferation due to depressed expression of CD25.