Oftalmol Zh.2015;3:69-75
«Migratory» phenotype of lymphocytes in peripheral blood in patients with uveal melanoma in varying efficiency preserving therapy
L. Velichko
SI «The Filatov Institute оf Eye Diseases аnd Tissue Therapy NAMS оf Ukraine», Odessa (Ukraine)
Provided by a whole complex of signals — one of them is the most significant signal coming from IL-2 as well as chemokines such as RANTES that are not only chemoattractant but also inactivator of T — cells. All these effects lead to activation of lymphocytes, which compared to resting one can cross the blood-barrier.
The aim of this study was to investigate the relationship between «immigration» and lymphocyte phenotype marker of apoptosis and progression of uveal melanoma in organ-preserving treatment.
Material and methods. A histoimmunocytochemical method by using monoclonal antibodies compared the level of expression CD54+ and CD95+ lymphocytes in the peripheral blood of patients with uveal melanoma with different efficacy of organ preserving treatment. Depending on the outcome of treatment (photocoagulation + ?-Application therapy) there were formed two groups: 116 patients with tumor regression, and 34 patients with progressive growth and subsequent enucleation of the eye. The statistical processing has been done with the help of the program (Statistica 7.0 ).
Results. Significant differences were observed in patients with uveal melanoma with different efficacy of organ preserving treatment in absolute and relative values of CD54 + and CD95+. In tumor regression the absolute value of the expression level of the marker CD54+ in the peripheral blood lymphocytes was (278.3 (183.9)) cells / mcl and relative value — (19.2 (9.2)) % relative to the absolute (190.0 (129.5)) cells / mcl and relative (14.9 (7.1)) % value in patients with progressive tumor growth (p1 = 0.03 and p2= 0.04, respectively). The absolute value of the expression level of the marker of apoptosis CD95+ in patients with uveal melanoma with tumor regression was (325.2 (206.3)) cells / mcl, and the relative value of — (21.8 (9.6)) % relative to the absolute (218 6 (133.8))cell/mcl, and a relative value (16.2 (6.3)) % in tumor progression (P1 = 0.02 and P2 = 0.01, respectively). To preserve the eye during the treatment is extremely important to regulate highly activated T -cells and suppression of the immune response to the blocking of inflammation by means of an excess of apoptosis (CD95 +).
Conclusion. The level of expression of the molecular markers of activation CD54+ and CD95+ in patients with regression of uveal melanoma was significantly higher than in the patients with progressive tumor growth and subsequent enucleation after organ preserving treatment.
Key words: uveal melanoma, molecular markers of activated lymphocytes predict treatment outcome.
References
Velichko LN, Maletskii AP, Polyakova SI, Chebotarev EP, Spirko VK. Changes in the level of early and late markers of activation of lymphocytes in patients with uveal melanoma in the organ-preserving treatment. Theses of scientific conference «Modern achievements in ophthalmology». Kiev. 9–10 November 2010. 135–137. In Russian.
Velichko LN. The level of expression of molecular markers of activation of peripheral blood lymphocytes in patients with uveal melanoma with varying efficiency organ-preserving treatment. Oftalmol Zh. 2013;5:9–13. In Russian.
Crossref
Crossref
Vit VV. Photocoagulation changees of uveal melanomas. Arkh. Patol. 1985;47(7): 23–29. In Russian.
Vit VV. Uveal melanoma cell photosensitivity by ionizing radiation. Oftalmol Zh. 1990;8:484–489. In Russian.
Vit VV. Tumor pathology of visual organ. Odessa: Astroprint; 2009. 610 p.
Vit VV. Pathologic anatomy and treatment pathomorphosis of pigmented tumors in uveal tract of the human eye: author’s thesis for Doc. Of Med. Sc.: 14.03.02 «Pathologic anatomy». Odessa. 1987. 30 p.
Vit VV. The prognostic value of morphological features of immune response in uveal melanoma of different cell types. Arkh. Patol. 1983;7:25–30. In Russian.
Gluzmad DF, Sklyarenko LM, Nadgornaia VA, Kryachok IA. Diagnostic immunocytochemistry of tumors. Kiev: Morion; 2003. 6–15.
Khaitov RM. Physiology of the immune system. M.: VINITI RAN; 2005. 375 p.
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):1865–1872.
Cross AH. Immune cell traffic control and the central nervous system. Semin. Neurosci. 1992;4:213–219.|
Crossref
Crossref
Durie FH, Campbell AM, Lee WR, Damato BE. Analysis of lymphocytic infiltration in uveal melanoma. Invest. Ophthalmol. Vis. Sci. 1990;31: 2106–2110.
G?llnitz R, Lommatzsch PK. Zur prognostischen Bedeutung der lymphozyt?ren Infiltration beim malignen Melanom der Aderhaut. Klin. Monbl. Augenheilkd. 1988;192(6):660–665.
Crossref
Crossref
Herron GS, Werb Z, Dwyer K, Banda MJ. Secretion of metalloproteinases by stimulated capillary endothelial cells. J. Biol. Chem. 1986;261(6):2810–2813.
Lenardo M, Chan KM, Hornung F et al. Nature T-lymphocyte apoptosis. Immune regulation in a dynamic and unpredictable antigenic environment. Annu Rev. Immunol. 1999;17:221–253.
Crossref
Crossref
Makitie T, Summanen P, Tarkkanen A, Kivela T. Microvascular loops and networks as prognostic indicators in choroidal and ciliary body melanomas. J. Nat. Cancer Inst. 1999;91:359–367.
Crossref
Crossref
Makitie T, Summanen P, Tarkkanen A, Kivela T. Tumor-infiltrating macrophages (CD68(+) cells) and prognosis in malignant uveal melanoma. Invest. Ophthalmol. Vis. Sci. 200;42(7):1414–1421.
Pryce G, Male D, Campbell I, Greenwood J. Factors controlling T-cell migration across rat cerebral endothelium in vitro. J. Neuroimmunol. 1997;75:1(2):84–94.
Rath PC, Aggarwal BB. TNF-induced signaling in apoptosis. J. Clin. Immunol. 1999;104:1021–1029.
Tobal K, Deuble K, McCartney A. Characterization of cellular infiltration in choroidal melanoma. Melanoma. Res. 1993;3(1):63–65.
Velichko LN, Maletskiy AP, Vit VV, Chebotaryov YP. The dynamics of molecular markers expression of blood lymphocytes activating at patients with an uveal melanoma at the different types of treatment. Challenges in Ophthalmology 109. Dog-Congress 29.9–2.10.2011 Estrel, Berlin. (PS 23–219).
Velichko LN, Maletskiy AP, Vit VV. The dynamics of molecular markers expression of blood lymphocytes activating at patients with an uveal melanoma at the different types of treatment. Congress The European Association for Vision and Eye Research (EVER) Science for Sight. Nice, October 10–13, 2012. 83.