Oftalmol Zh.2015;2:44-48


Prediction the results of ablative treatment in patients with uveal melanoma using molecular markers of lymphocyte activation

L. N. Velichko, A. P. Maletsky, V. V. Vit, A. V. Bogdanova

SI «The Filatov Institute of Eye Diseases and Tissue Therapy NAMS of Ukraine»

Abstract. One approach to predicting the outcome of ablative treatment is the study of the expression of molecular markers of lymphocyte activation. Changing the level of expression of receptors on the cell surface reflects the processes in the body. The purpose — to explore the possibility of predicting the results of ablative treatment using molecular markers of lymphocyte activation.

A comparative analysis of the expression of lymphocyte activation molecular markers was made in 150 patients with uveal melanoma. The expression level of molecular markers of lymphocyte activation CD54+ and CD95+ was studied using monoclonal antibodies by histoimunocytochemical method on peripheral blood lymphocytes. I group (116 patients) — patients with uveal melanoma regression after photocoagulation and ?-therapy; II group (34 patients) — patients with progressive tumor growth and subsequent removal of the eye.

The study evaluated informative predictability of lymphocyte activation molecular markers CD54+ and CD95+ to assess possible to determine the level of markers for predicting success of ablative treatment. ROC-analysis (Receiver Operating Characteristic analysis) showed that molecular markers of lymphocyte activation CD54+ and CD95+ were the most informative. Thresholds expression level was defined on peripheral blood lymphocytes CD54+ (above 171 cells/ml — absolute level) and CD95+ (above 282 cells/ml — absolute level); CD54+ (above 19% — relative level) and CD95+ (above 18% — relative level), predicts regression of melanoma in 77,2% of cases. Expression lymphocyte activathion molecular markers CD54+ and CD95+ below this level allows to predict subsequent tumor growth in 70,5% of cases.

Key words: uveal melanoma, molecular markers of lymphocyte activation, prediction result of treatment


  1. Berezhnaia NM. The role of immune system cells in the tumor microenvironment. II. The interaction of cells of the immune system with the other components of the microenvironment. Onkologiia. 2009;11(2):86–93/ In Russian. 
  2. Gluzman DF, Sklyarenko LM, Nadgornaia VA, Kryachok IA. Diagnostic immunocytochemistry of tumors. Kiev:Morion; 2003. 6–15. 
  3. Kozlov IG, Gorlina NK, Cheredyeyeva AN. Receptors of contact interaction. Immunologiia. 1995;4:14–26. In Russian. 
  4. Blank C, Kuball J, Voelkl S et al. Blockade of PD — L1 (B7 — H1) augments human tumor-specific T cell responses in vitro. Int. J. Cancer. 2006;119(2):317–27. 
    Crossref   Pubmed
  5. Blom DJ, Luyten GP, Mooy C et al. Human leukocyte antigen class I expression. Marker of poor prognosis in uveal melanoma. Invest. Ophthalmol. Vis. Sci. 1997; 38(9):1865–72. 
  6. De Waard-Siebinga I, Hilders CG, Hansen B E. HLA expression and tumor — infiltrating immune cells in uveal melanoma. Arch. Clin. Exp. Ophthalmol. 1996; 234(1):34–42. 
    Crossref   Pubmed
  7. Fidler IJ, Poste G. The «seed and soil» hypothesis revisited. Lancet Oncol. 2008;9(8):808. 
    Crossref   Pubmed
  8. Fridman WH, Galon J, Pages F et al. Prognostic and predictive impact of intra and peritumoral immune infiltrates. Cancer Res. 2011; 71(17):5601–5. 
    Crossref   Pubmed
  9. Jameson SC, Bevan MJ. T cell receptor antagonists and partial agonists. Immunity. 1995:2(1):1–11. 
    Crossref   Pubmed
  10. Makitie T, Summanen P, Tarkkanen A, Kivela T. Tumor-infiltrating macrophages (CD68(+) cells) and prognosis in malignant uveal melanoma. Invest. Ophthalmol. Vis. Sci. 2001; 42(7):1414–21. 
  11. Mantovani A, Romero P, Palucka AK, Marincola FM. Tumour immunity: effector response to tumour and role of the microenvironment. Lancet. 2008; 371:771–83. 
  12. Shaw A S. Making the T cell receptor go the dis — tance: a topological view of T cell activation / A. S. Shaw, M. L. Dustin // Immunity. — 1997:6. — P. 361–369. 
  13. Singh AD, Shields CL, Shields JA. Prognostic factors in uveal melanoma. Melanoma Res. 2001;11:255–63. 
  14. Vetter CS, Lieb W, Brocker EB, Becker JC. Loss of nonclassical MHC molecules MIC — A/B expression during progression of uveal melanoma. Br. J. Cancer. 2004;91(8):1495–9. 
  15. Wulfing C, Rabinowitz JD, Beeson C et al.. Kinetics and extent of T cell activation as measured with the calcium signal. J. Exp. Med. 1997; 185:1815–25.