Immunofluorescence-detected infiltration of CD4+FOXP3+ regulatory T cells is relevant to the prognosis of patients with endometrial cancer

Abstract

Objective: Host antitumor immune responses are associated with many types of immune cells and soluble components. In particular, CD8 cytotoxic T lymphocytes (CTLs) play a central role. Regulatory T cells (Tregs) have been reported to induce tumor immune tolerance in various cancers. In the present study, we evaluated lymphocytic infiltration in endometrial cancer tissue to clarify its relationship with clinicopathological factors and the prognosis of patients.

Methods: The study included 53 patients whose condition was diagnosed as endometrial cancer between 1994 and 2004 at Keio University hospital. Using formalin-fixed, paraffin-embedded specimens of the uterus, immunohistochemistry was performed with antihuman CD8, antihuman CD4, and antihuman FOXP3 primary antibodies, and the binding sites of the antibodies were visualized using fluorescence-conjugate secondary antibodies. CD4FOXP3 cells were identified as Tregs in this study. The numbers of CD8 cells, CD4 cells, and Tregs as well as the Treg/CD8 and Treg/CD4 ratios were analyzed to evaluate the relationship between clinicopathological factors and patient prognosis.

Results: Of the 53 patients studied, 50.9% of them had early-stage disease, 49.1% had advanced stage disease, 47.2% had well-differentiated cancer (grade [G] 1), 24.5% had moderately differentiated cancer (G2), and 28.3% had poorly differentiated cancer (G3). The CD8 and CD4 cell counts, Treg count, and Treg/CD8 and Treg/CD4 ratios were significantly higher in the patients with advanced poorly differentiated carcinomas and with positive lymphovascular space invasion than in those with early well-differentiated carcinomas and with negative lymphovascular space invasion. In disease-free survival, the prognosis of the patients with high Treg counts and Treg/CD8 ratios was significantly worse than that of the patients with low Treg counts and Treg/CD8 ratios (P < 0.05).

Conclusions: The Treg count and Treg/CD8 ratio may be new prognostic factors for endometrial cancer.