Velychko L. Immunopathogenetic mechanisms of advance tumour stage in uveal melanoma and its correction with organ-preserving treatment

The object - isuveal melanoma. The subject of the study isthe level of lymphocyte activation molecular markers expression, the state of antitumor immunity and their role in the implementation of the therapeutic effect in patients with uveal melanoma. The effectiveness of immunotherapy, including an interferon tiloron inducer, in immunoreabilitation of patients with uveal melanoma. Predictor value of lymphocyte activation molecular markers in predicting the result of organ-preserving treatment, cell type and uveal melanoma germination in sclera layers. The nature of the interaction of immune cells with cells of uveal melanoma in vitro. The aim of the study is to optimize the patients with uveal melanoma invasive therapeutic approach based on the study of the pathogenic molecular mechanisms of tumor progression, to determine the feasibility of immunocorrecting therapy in the organ-preserving treatment complex (photocoagulation + β-application therapy). Research methods are biomicroscopy, visual field, tonometry, sonarography, method of coculturing immune cells with melanoma cells, histo-anatomical, immunocytochemical, immunoenzymometric, statistical analysis methods. The studies conducted have shown that the combination therapy (photocoagulation + β-application therapy) provides for increased activity of the receptor apparatus of immunocompetent cells (СD7+, СD38+, СD45+, СD54+, СD95+, СD150+), enhancement of specialized functions of all lymphocyte populations involved in specific immune response. The studies conducted showed the possibility of prognosticating the positive result of organ-preserving treatment (complete, partial regression and stabilization of tumour growth) in uveal melanoma patients of 70,5% of cases based on the study of the expression level of intercellular adhesion molecule (ICAM-1) СD54+ and apoptosis molecule (FAS) СD95+ in peripheral blood lymphocytes. Further studies have shown the correctness of our hypothesis that in the melanoma invasion into sclera layers the histohemic barriers are breaking down with subsequent disruption of eye homeostasis and T cells activation. We have demonstrated that in sclera invasion patients the level of lymphocyte activation molecular markers expression (СD7+, СD25+, СD38+, СD45+, СD150+, the intercellular adhesion molecule (ICAM-1) СD54+ and apoptosis molecule (FAS) СD95+) is significantly higher than in patients with no invasion. The high prognosticative value was shown of determining the level of expression of the intercellular adhesion molecule (ICAM-1) СD54+ and apoptosis molecule (FAS) СD95+ for prognosticating the uveal melanoma invasion into the sclera layers. The combined identification of these markers allows prognosticating the uveal melanoma invasion into sclera layers in 76,5 % of cases. The possibility was identified of prognosticating the epithelioid cell type of uveal melanoma in 78,2 % of cases by the expression level of СD7+ and СD150+ lymphocytes activation molecular markers. Our study of tiloron effect in vitro on the expression state of the peripheral blood lymphocyte activation molecular markers in uveal melanoma patients showed a significant increase in the expression level of СD7+, СD25+, intercellular adhesion molecule (ICAM-1) СD54+ and apoptosis molecule (FAS) СD95+. The inclusion of interferon inducer tiloron in the complex of organ-preserving treatment (photocoagulation + β-application therapy) allowed to increase the expression level of the intercellular adhesion molecule (ICAM-1) СD54+, whereas in the control group showed no significant increase in the expression level of this molecule. Our study method of change in the lymphocytes molecular profile under the effect of various immunotropic drugs allowed finding an adequate immunological correction in uveal melanoma patients. The significance of study results for clinical practice is the development of multifactorial therapy (photocoagulation + β-application therapy), which includes tiloron and was the best strategy in treating large size melanomas. The results of the study are introduced into clinical practice of the Department of Ophthalmooncology of the SI "Filatov Institute of Eye Diseases and Tissue Therapy of the National Academy of Medical Sciences of Ukraine".