ELEVATION OF SERUM LEVELS OF SOLUBLE FORMS OF STRESS-INDUCED MOLECULES MICA IN ONCOLOGICAL DISEASES

E.V. Abakushina (1), A.V. Klinkova (2), L.M. Kanevskiy (2), E.I. Kovalenko (2)
1 -Medical Radiological Research Centre, Russian Federation, 249036, Kaluga region, Obninsk, Koroleva street, 4;
2 -M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry; Russian Federation, 117997, Moscow, GSP-7, Miklukho-Maklaya street, 16/10;

Introduction. Interactions of exposed on the tumor cell surface or circulating in the bloodstream molecules MICA with activating receptor NKG2D play an important role in the regulation of antitumor immune response. Accumulation of soluble MICA compromises NKG2D- dependent cytotoxicity and may lead to escape of tumors from immune surveillance. The aim of the study. The comparative analysis of serum levels of MICA of various malignant patients and healthy volunteers. Materials and methods. Serum levels of stress-induced molecules MICA of 60 healthy donors and 242 patients with various malignant diseases were measured by ELISA. Flow cytometry analysis of peripheral blood lymphocytes composition, NKG2D expression and cytotoxic activity was performed for a number of patients and healthy volunteers. Results. Low amounts of MICA (mean: 29–76 pg/ml) were detected in sera of thyroid cancer, bladder cancer, prostate cancer and Hodgkin disease patients. A significant increase of serum MICA levels comparing with the control group was revealed in groups of patients with non-Hodgkin lymphoma, laryngopharyngeal, breast, cervical, stomach and colorectal cancers (mean: 140-291 pg/ml). The maximal soluble MICA values (>1000 pg/ml) were recorded in groups of patients with melanoma and non-Hodgkin lymphoma. Serum MICA levels were negatively correlated with the expression of NKG2D on the lymphocyte surface. Conclusions. The amount of soluble MICA in the circulation increased in certain types of cancer. It can result in reduced expression of the receptor NKG2D, decline of the functional activity of cytotoxic lymphocytes and exacerbation of the disease.
Keywords: 
malignant diseases, stress-induced molecule MICA, natural killer cells, receptor NKG2D