The Distribution And Significance Of Regulatory T Cells In Peripheral Blood And Tumor Micorenviroment Of Papillary Thyroid Carcinoma Patients

Objective:Explore the distribution of regulatory T cells (Treg) of papillary thyroid carcinoma patients in peripheral blood and tumor microenvironment, and investigate the relationship between Treg cells and clinicopathologic factors of papillary thyroid carcinoma patients. Meanwhile, the distribution of Treg cells was investigated in the peripheral blood and tumor microenvironment of papillary thyroid carcinoma associated with Hashimoto’s thyroiditis patients.Methods:1. From February2013to March2013, the peripheral blood samples of69cases of papillary thyroid carcinoma were collected from Department of Thyroid and Neck Tumor, Tianjin Medical University Cancer Institute and Hospital. And23nodular goiter patients were enrolled as controls. Flow cytometry was used to detect the expression of CD4+CD25+CD127low/-regulatory T cells. Then, we investigated the distribution of CD4+CD25+CD127low/-Treg in the peripheral blood and analyzed the relationship between Treg and clinicopathologic factors. Meanwhile, the distribution of Treg was investigated in the peripheral blood of papillary thyroid carcinoma associated with Hashimoto’s thyroiditis patients.2. From July2011to September2011, the paraffin blocks of104cases of papillary thyroid carcinoma were collected from Department of Thyroid and Neck Tumor, Tianjin Medical University Cancer Institute and Hospital. And30nodular goiter patients were enrolled as controls. Foxp3-positive Treg were detected by immunohistochemistry in the tumor microenvironment. Then, we analyzed the relationship between the expression of Foxp3in the tumor microenvironment and clinicopathologic factors. The expression of Foxp3was investigated in the tumor microenvironment of papillary thyroid carcinoma associated with Hashimoto’s thyroiditis patients.Results:1. There was a significantly higher proportion of CD4+CD25+CD127low/-Treg in the peripheral blood of papillary thyroid carcinoma patients than that in nodular goiter patients.2. The higher percentage of CD4+CD25+CD127low/-Treg in the peripheral blood of PTC patients was significantly associated with extrathyroid extension and lymph node metastasis (P<0.05). The proportion of CD4+CD25+CD127low/-Treg was significantly lower in PTC patients with HT than in patients without HT (P<0.05).3. Foxp3+lymphocytes were observed both in PTC and metastasis lymph nodes tissues, whereas were absent in nodular goiter tissues.4. The higher expression of Foxp3in the tumor microenvironment of PTC patients was significantly associated with extrathyroid extension and lymph node metastasis(P<0.05). Although it was not statistically significant, PTC with HT patients tented to have higher expression of Foxp3.Conclusion:1. The proportion of CD4+CD25+CD127low/-Treg in the peripheral blood of papillary thyroid carcinoma patients was significantly higher than that in nodular goiter patients. Foxp3+lymphocytes were observed both in PTC and metastasis lymph nodes tissues, whereas were absent in nodular goiter tissues.2. The higher percentage of CD4+CD25+CD127low/-Treg in the peripheral blood and higher expression of Foxp3in the tumor microenvironment of PTC patients were significantly associated with extrathyroid extension and lymph node metastasis. Treg may participate in tumor immune escape, and contribute to progress and metastasis of PTC.3. The proportion of CD4+CD25+CD127low/-Treg in the peripheral blood was significantly lower in PTC patients with HT, whereas the expression of Foxp3in the tumor microenvironment tented to be higher in PTC patients with HT than that in patients without HT. These findings suggest a compensatory expansion of Treg at the site of inflammation in tissues of PTC with HT to suppress the immune response.