Regulatory T Cells in Peripheral Blood, Lymph Node, and Thyroid Tissue in Patients with Medullary Thyroid Carcinoma

Abstract

Immunological response of the human body is controlled by the suppressive characteristics of regulatory T cells (Tregs). In various diseases a change in the number of Tregs is evident. For example, whereas Tregs are reduced in auto-immunological processes, an increase of Tregs is found with various malignant tumors. Regarding medullary thyroid carcinoma (MTC) no such studies have been performed to date. Expression of CD4 and CD25 in CD45+ leukocytes from blood and lymph nodes was studied by flow cytometry in patients with MTC and patients with benign goiter. We also examined the marker forkhead box P3 (FoxP3), an intracellular transcription factor, which is supposed to be the most specific marker for Tregs. Immunohistochemical staining for FoxP3 was performed on lymph node and thyroid tissue. The number of FoxP3+ lymphocytes in peripheral blood was significantly higher in patients with MTC than in controls (p = 0.02). This result was confirmed immunohistochemically in lymph node and thyroid tissue, as well as in carcinoma tissue. No difference in CD4+CD25+ lymphocytes was observed between the two groups. After clinical staging (International Union against Cancer-UICC-stages) of MTC patients, triplication of FoxP3+ lymphocytes could be observed from MTC < UICC II to MTC > UICC II. An increase of FoxP3+ lymphocytes could be shown in peripheral blood of patients with MTC but not in patients with benign goiter; this increase also correlates with findings in lymph nodes and thyroid gland. The number of FoxP3+ cells correlated with the patients' prognosis. Therefore, FoxP3+ lymphocytes are a good diagnostic criterion for malignancy in patients with medullary thyroid carcinoma, and their presence at staging may influence therapeutic decisions.