The Soluble Major Histocompatibility Complex Class I-Related Chain A (sMICA) Protein Reduced NKG2D Expression On NK And T Cells In Patients With Pituitary Adenoma

Background: Pituitary adenoma is one of the most common intracranial tumors, following intracranial glioma and meningioma. NK and CD8~+ T cells play an important role in eliminating virus-infected and tumor cells through NKG2D activating receptors, which can improve the lysis of target cells by binding with the major histocompatibility complex class I-related chain A (MICA) proteins. Increased serum levels of MICA have been found in patients with the tumors and NKG2D/MICA pathway exists in epithelial tumors. The aim of this study is to compare the levels of soluble MICA (sMICA) and NKG2D-expressing NK and T cells in blood samples from patients with prolactinomas and nonsecreting pituitary adenoma and those from healthy donors and find the immunologic escape of pituitary adenoma.Methods: 23 patients with nonsecreting pituitary adenoma, 16 patients with prolactinomas, 17 healthy donors which were admitted in Department of Neurosurgery, Qilu Hospital of shandong university from March 2008 to November 2008.Peripheral blood with heparin was collected to obtain mononuclear cells in methods of Red cell lysis buffer and Lymphocytes Separation Medium in patients with nonsecreting pituitary adenoma and prolactinomas and healthy donors. Peripheral blood without heparin was collected to obtain sera through centrifugation in patients with nonsecreting pituitary adenoma and prolactinomas and healthy donors.The correspondent tissue of pituitary adenoma and five of the normal brain tissue were also collected. K562 cells were cultured, which was used in cytotoxicity assays.NKG2D-expressing NK and T cells were analyzed by flow cytometry. Serum sMICA levels were measured by ELISA. Also, a correlation analysis was made to associate sMICA levels with NKG2D expression. The expression of MICA in part of the correspondent tissues and normal brain tissue was examined by means of reverse transcription-polymerase chain reaction (RT -PCR). The ctotoxicity assays detected NK activity to K562 cells in patients with nonsecreting pituitary adenoma and healthy donos.Results: We found a decrease in the fluorescence intensity of NKG2D-expressing NK in prolactinoma and non-secreting pituitary adenoma groups and in the number and fluorescence intensity of NKG2D-expressing T cells compared with those from the healthy donors. Significant amounts of sMICA were detected in sera from nearly all patients. Pearson analysis showed a negative correlation between sMICA and NKG2D-expressing cells. The expression of MICA existed in tumors with prolactinoma and non-secreting pituitary adenoma but not in normal brain tissue. The ctotoxicity assays found a decrease in NK activity in patients with nonsecreting pituitary adenoma compared with healthy donors.Conclusion: Our results demonstrate for the first time the expression of MICA in tumors with prolactinoma and non-secreting pituitary adenoma and high sMICA levels in sera from patients with pituitary adenoma compare with those from healthy donors. We also observed a diminution in the number of NKG2D-expressing T cells in the patient samples due to sMICA. We concluded that sMICA could reduce the expression of NKG2D on NK and T cells and the activity of NK and T cells. The immune-escape of pituitary adenoma probably could be relative to the down-regulation of NKG2D and the up-regulation of its ligand MICA.