Antitumor action of lymphokin-activated сеlls of patients with soft tissue sarcomas and melanomas in dependence on expression of MHC classes I and II antigenes

Aim: To study expression of major histocompatibility complex (MHC) classes І and ІІ antigens and CD25, CD71, Ki-67, CD54, CD56, CD11b, PCNA on lymphocytes and tumor cells and antitumor action of lymphocytes activated with IL-2. Materials and Methods: Tumor explants (soft tissue sarcoma, n = 20, mela...

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Дата:2006
Автори: Berezhnaya, N.M., Vinnichuk, U.D., Belova, O.B., Baranovich, V.V.
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Опубліковано: Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України 2006
Назва видання:Experimental Oncology
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Цитувати:Antitumor action of lymphokin-activated сеlls of patients with soft tissue sarcomas and melanomas in dependence on expression of MHC classes I and II antigenes / N.M. Berezhnaya, U.D. Vinnichuk, O.B. Belova, V.V. Baranovich // Experimental Oncology. — 2006. — Т. 28, № 3. — С. 231-234. — Бібліогр.: 22 назв. — англ.

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spelling irk-123456789-1375702018-06-18T03:06:35Z Antitumor action of lymphokin-activated сеlls of patients with soft tissue sarcomas and melanomas in dependence on expression of MHC classes I and II antigenes Berezhnaya, N.M. Vinnichuk, U.D. Belova, O.B. Baranovich, V.V. Original contributions Aim: To study expression of major histocompatibility complex (MHC) classes І and ІІ antigens and CD25, CD71, Ki-67, CD54, CD56, CD11b, PCNA on lymphocytes and tumor cells and antitumor action of lymphocytes activated with IL-2. Materials and Methods: Tumor explants (soft tissue sarcoma, n = 20, melanoma, n = 25) were co-cultivated in diffusion chambers with autologous lymphocytes; antitumor action was evaluated by morphologic patterns of explant’s growth. Expression of CD25, CD71, Ki-67, CD54, CD56, CD11b, PCNA was evaluated by the method of indirect fluorescence using respective monoclonal antibodies. Results: The highest antitumor action of lymphocytes toward soft tissue sarcoma and melanoma cells is observed if tumor cells are expressing MHC class I antigens. In the cases of soft tissue sarcoma no correlation between the level of antitumor activity of lymphocytes and expression of CD25, CD71, Ki-67, CD54, CD56, CD11b, PCNA has been found, whilst in the case of melanoma it is associated with the high level of CD11b expression. Conclusion: There is a direct correlation between sensitivity of soft tissue sarcoma and melanoma cells to action of lymphokin-activated killer cells and the level of MHC class I antigens. Цель: изучить экспрессию антигенов І и ІІ класса главного комплекса гистосовместимости (ГКГ) на лимфоцитах и опухолевых клетках (саркомы мягких тканей и меланома кожи) и противоопухолевое действие лимфоцитов, активированных и неактивированных ИЛ-2 параллельно с экспрессией некоторых рецепторов, характеризующих протеом. Материалы и методы: культивирование эксплантатов опухоли и аутологичных лимфоцитов в диффузионных камерах с дальнейшим изучением противоопухолевого действия лимфоцитов на основании морфологических особенностей роста эксплантатов. Экспрессию антигенов CD25, CD71, Ki-67, CD54, CD56, CD11b, ядерного антигена пролиферирующих клеток (ИПО-38) определяли методом непрямой флуоресценции с помощью соответствующих моноклональных антител. Результаты: наиболее выраженное противоопухолевое действие лимфоцитов как больных саркомами мягких тканей, так и меланомой проявляется по отношению к тем опухолевым клеткам, которые экспрессируют антигены I класса ГКГ. Установлено, что значение экспрессии указанных структур для противоопухолевого действия зависит от биологических особенностей опухоли: зависимости между уровнем противоопухолевой активности и экспрессией изученных рецепторов клетками больных саркомой не выявлено. В то же время наиболее выраженное противоопухолевое действие лимфоцитов больных меланомой сочеталось с высоким уровнем экспрессии ими CD11b. Выводы: установлена прямая зависимость чувствительности опухолевых клеток к действию лимфокинактивированных клеток от уровня экспрессии антигенов ГКГ I класса на клетках как меланомы, так и сарком. 2006 Article Antitumor action of lymphokin-activated сеlls of patients with soft tissue sarcomas and melanomas in dependence on expression of MHC classes I and II antigenes / N.M. Berezhnaya, U.D. Vinnichuk, O.B. Belova, V.V. Baranovich // Experimental Oncology. — 2006. — Т. 28, № 3. — С. 231-234. — Бібліогр.: 22 назв. — англ. 1812-9269 http://dspace.nbuv.gov.ua/handle/123456789/137570 en Experimental Oncology Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
institution Digital Library of Periodicals of National Academy of Sciences of Ukraine
collection DSpace DC
language English
topic Original contributions
Original contributions
spellingShingle Original contributions
Original contributions
Berezhnaya, N.M.
Vinnichuk, U.D.
Belova, O.B.
Baranovich, V.V.
Antitumor action of lymphokin-activated сеlls of patients with soft tissue sarcomas and melanomas in dependence on expression of MHC classes I and II antigenes
Experimental Oncology
description Aim: To study expression of major histocompatibility complex (MHC) classes І and ІІ antigens and CD25, CD71, Ki-67, CD54, CD56, CD11b, PCNA on lymphocytes and tumor cells and antitumor action of lymphocytes activated with IL-2. Materials and Methods: Tumor explants (soft tissue sarcoma, n = 20, melanoma, n = 25) were co-cultivated in diffusion chambers with autologous lymphocytes; antitumor action was evaluated by morphologic patterns of explant’s growth. Expression of CD25, CD71, Ki-67, CD54, CD56, CD11b, PCNA was evaluated by the method of indirect fluorescence using respective monoclonal antibodies. Results: The highest antitumor action of lymphocytes toward soft tissue sarcoma and melanoma cells is observed if tumor cells are expressing MHC class I antigens. In the cases of soft tissue sarcoma no correlation between the level of antitumor activity of lymphocytes and expression of CD25, CD71, Ki-67, CD54, CD56, CD11b, PCNA has been found, whilst in the case of melanoma it is associated with the high level of CD11b expression. Conclusion: There is a direct correlation between sensitivity of soft tissue sarcoma and melanoma cells to action of lymphokin-activated killer cells and the level of MHC class I antigens.
format Article
author Berezhnaya, N.M.
Vinnichuk, U.D.
Belova, O.B.
Baranovich, V.V.
author_facet Berezhnaya, N.M.
Vinnichuk, U.D.
Belova, O.B.
Baranovich, V.V.
author_sort Berezhnaya, N.M.
title Antitumor action of lymphokin-activated сеlls of patients with soft tissue sarcomas and melanomas in dependence on expression of MHC classes I and II antigenes
title_short Antitumor action of lymphokin-activated сеlls of patients with soft tissue sarcomas and melanomas in dependence on expression of MHC classes I and II antigenes
title_full Antitumor action of lymphokin-activated сеlls of patients with soft tissue sarcomas and melanomas in dependence on expression of MHC classes I and II antigenes
title_fullStr Antitumor action of lymphokin-activated сеlls of patients with soft tissue sarcomas and melanomas in dependence on expression of MHC classes I and II antigenes
title_full_unstemmed Antitumor action of lymphokin-activated сеlls of patients with soft tissue sarcomas and melanomas in dependence on expression of MHC classes I and II antigenes
title_sort antitumor action of lymphokin-activated сеlls of patients with soft tissue sarcomas and melanomas in dependence on expression of mhc classes i and ii antigenes
publisher Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
publishDate 2006
topic_facet Original contributions
url http://dspace.nbuv.gov.ua/handle/123456789/137570
citation_txt Antitumor action of lymphokin-activated сеlls of patients with soft tissue sarcomas and melanomas in dependence on expression of MHC classes I and II antigenes / N.M. Berezhnaya, U.D. Vinnichuk, O.B. Belova, V.V. Baranovich // Experimental Oncology. — 2006. — Т. 28, № 3. — С. 231-234. — Бібліогр.: 22 назв. — англ.
series Experimental Oncology
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AT belovaob antitumoractionoflymphokinactivatedsellsofpatientswithsofttissuesarcomasandmelanomasindependenceonexpressionofmhcclassesiandiiantigenes
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fulltext Experimental Oncology 28, 231–234, 2006 (September) 231 Expression of MHC of classes I and II antigens is one of the major characteristics of lymphocytes and tumor cells. As a rule, different alterations of the genes coding these antigens are leading to the disturbance of their functioning or significantly affect immuno- logic response. That’s explaining why the patterns of genotype of lymphocytes and tumor cells, in particular expression of MHC antigens plays significant role in recognition of tumor antigens with the following lysis of tumor cells. Such statement is proved in a number of studies, at the first hand - in classic works of R. Zinker- nagel [1, 2] where it is reported that immunological response occurs only upon expression of the same MHC alleles on lymphocytes and tumor cells. In the last years a number of publications are arguing that efficacy of immunotherapy depends on expression of the alleles of MHC antigens that repre- sent discrete peptides of tumor cells in each concrete case. For example, it was shown that such peptides of prostate cancer cells are represented by HLA-A24, and particularly these molecules are inducing specific immune response if tumor cells express HLA-A24 [3]. Similar data were received in the research of specific response of T-lymphocytes of patients with gastric cancer; these lymphocytes are lyzing tumor cells if both types of the cells express HLA-A2 or HLA-A24 antigens [4]. An important role in interactions between lympho- cytes and tumor cells belongs to the patterns of their proteome composed from a variety of receptor and antigens, each of which is controlled by respective genes. Disturbance of their functions results in pro- teome alterations. Realization of cytotoxic action depends on expres- sion of MHC classes I and II antigens and patterns of proteome; however, the question — at what degree such dependence affects the efficacy of cytotoxic action of lymphokin-activated cells (LAK) — requires further examination. At the same time, adoptive immu- notherapy of cancer with the use of LAK is known to oc- cupy one of the central places in cancer imunotherapy. Presently the use of IL-2 for activation of lymphocytes is the mostly widely used approach [5, 6]. Since the first report on LAK-phenomenon, it became the subject of active studies (phenotypic characteristics of LAK cells, intensity of their killer activity, patterns of action of LAK isolated from different subpopulations of cells, research of LAK migration in the body). However, the results are contradictory, possibly due to application of different approaches for generation of LAK (doses of IL-2, terms of cultivation, the sourse of lymphocytes, their phenotype etc) [7–9]. As it is mentioned above, the role of patterns of LAK phenotype and tumor cells in their interaction remained poorly studied yet; but single reports are demonstrating that therapeutic effect of immuno- therapy with the use of IL-2-activated LAK depends on phenotype of these cells, too [10]. However, in one cases expression of MHC antigens has been studied only on tumor cells, in other cases — only on LAK. So, it looks reasonable to study the role of expression of MHC antigens and other components of proteome by tumor cells and LAK for their interaction. The first stages of interaction between LAK and target cells is the expression of adhesion molecules CD11a/CD18, CD54; in some publications it has been reported that the expression of mentioned proteins and MHC class I antigens occurs simultaneously Antitumor Action oF lymphokin-ActivAted сеlls oF pAtients with soFt tissue sArcomAs And melAnomAs in dependence on expression oF mhc clAsses i And ii Antigenes N.M. Berezhnaya*, U.D. Vinnichuk, O.B. Belova, V.V. Baranovich R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, National Academy of Sciences of Ukraine, Kyiv 03022, Ukraine Aim: To study expression of major histocompatibility complex (MHC) classes І and ІІ antigens and CD25, CD71, Ki-67, CD54, CD56, CD11b, PCNA on lymphocytes and tumor cells and antitumor action of lymphocytes activated with IL-2. Materials and Methods: Tumor explants (soft tissue sarcoma, n = 20, melanoma, n = 25) were co-cultivated in diffusion chambers with autologous lymphocytes; antitumor action was evaluated by morphologic patterns of explant’s growth. Expression of CD25, CD71, Ki-67, CD54, CD56, CD11b, PCNA was evaluated by the method of indirect fluorescence using respective monoclonal antibodies. Results: The highest antitumor action of lymphocytes toward soft tissue sarcoma and melanoma cells is observed if tumor cells are expressing MHC class I antigens. In the cases of soft tissue sarcoma no correlation between the level of antitumor activity of lymphocytes and expression of CD25, CD71, Ki-67, CD54, CD56, CD11b, PCNA has been found, whilst in the case of melanoma it is associated with the high level of CD11b expression. Conclusion: There is a direct correlation between sensitivity of soft tissue sarcoma and melanoma cells to action of lymphokin-activated killer cells and the level of MHC class I antigens. Key Words: class I and II MHC antigens, LAK, soft tissue sarcoma, melanoma. Received: August 7, 2006. *Correspondence: E-mail: berezh@onconet.kiev.ua Abbreviations used: IL — interleukin; LAK – lymphokin-activated killer cells; CTL – cytotoxic lymphocytes; MoAbs – monoclonal antibodies; PBL – peripheral blood lymphocytes; INF – interferon; MHC – major histocompatibility complex. Exp Oncol 2006 28, 3, 231–234 232 Experimental Oncology 28, 231–234, 2006 (September) [11, 12]. The role of expression of ICAM-1 (CD54), in particular on tumor cells for interaction with LAK has been shown also by other studies [13], that demon- strated that application of retinoid acid — compound increasing expression of the gene controlling ICAM-1 expression in tumor cells — resulted in elevation of sensitivity of tumor cells to action of LAK. Melanoma cells expressing MHC antigens became more sensitive to lyzis with LAK [14]; transfection of human ovarian cancer cells SKOV3 with IL-2 gene leads to significantly increased expression of HLA-ABC, HLA-DR, HLA-DQ molecules [15]. The role of MHC antigens expression on tumor cells and their positive or negative regulation may sig- nificantly depend on phenotype of cells, that possess cytotoxicity. In particular, it was shown that treatment of tumor cells with INFγ may lead to suppression of action of LAK obtained from natural killer cells; ex- pression of such MHC class I molecules as 1a and 1b suppresses cytotoxicity, and such inhibition may be abolished by treatment with antibodies against mentioned antigens [16]. The present work, is aimed on the study of MHC antigens expression on tumor cells as well on LAK in parallel with detection of the expression of some receptors, that may play role in LAK-dependent lysis. There were two main tasks: 1) to evaluate possible relation between expression of MHC class I and II antigens on lymphocytes and tumor cells (soft tissue sarcomas and skin melanomas) and antitumor action of non-activated and IL-2-activated lymphocytes; 2) to study the role of expression of some receptors for realization of antitumor action of LAK. mAteriAls And methods In the work tumor cells and PBL of 20 patients with soft tissue sarcoma (liposarcoma (n = 2), rhab- domyosarcoma (n = 2), fibrosarcoma (n = 3), syno- vial sarcoma (n = 6), inclassified sarcoma, (n = 2), angyoleiomyosarcoma (n = 2), malignant mesinchy- moma, neurosarcoma (n = 1), angyosarcoma (n = 1), malignant giant cell sarcoma (n = 1)) and 25 patients with melanoma cured in the Institute of Oncology, AMS of Ukraine (Kyiv, Ukraine) were used. The patients were 15–79 years old; from 20 cases with soft tissue sarcoma, 8 patients were at the II stage of the disease, 10 — at III stage, 2 — at IV stage; from 25 melanoma cases, 15 patients were at І, ІІ stages, 10 — at ІІІ and IV stages. PBL were isolated from heparinized blood by centrifugation in Ficoll-urograffin gradient (ρ = 1.077). Isolated tumor cells were obtained by enzymatic dis- aggregation of tumor tissue with 2 mg/ml collagenase (Sigma, USA) and 1 ng/ml DNAse (Sigma, USA) for 40 min at 37 ˚С. Expression of MHC classes I and II antigens, adhe- sion molecule CD54, transferrine CD71, interleukine-2, CD25, CD54, CD56, CD11b, antigen of proliferation Кі-67, nuclear antigen of proliferation on tumor cells and lymphocytes from patients was studied by the method of indirect fluorescence using respective monoclonal antibodies (MoAbs) (Medbiospecter, Rus- sia; DacoCytomation, Denmark; MoAb IPO-38, IEPOR NAS, Kiev, Ukraine). Antitumor activity of lymphocytes was studied by their co-cultivation with tumor cells in diffusional chambers [17] with the following morpho- logical examination of the samples. results And discussion Comparative evaluation of antitumor action of acti- vated (LAK) and non-activated lymphocytes of the pa- tients with soft tissue sarcoma has shown that PBL are characterized by expression of high level MHC class I antigens and low level — of class II, whilst IL-2 does not alter significantly their expression levels. Upon influence of IL-2, expression of CD25 varied in a wide range; that fact may be explained by individual patterns of lymphocytes of these patients (Table 1). On the base of the results of studied interactions between tumor cells and PBL, the patients were grouped as follow: 1) patients possessing PBL and LAK with marked antitumor activity, 2) patients possessing PBL and LAK without antitumor activity. Table 1. Expression of MHC class І and ІІ by activated (LAK) and not activated (PBL) lymphocytes and tumor cells of patients with soft tissue sarcoma Marker Antitumor activity (% cells) + – PBL LAK TC PBL LAK TC HLA-ABC 78.7 ± 7.3 80.4 ± 3.0 28.5 ± 6.8 71.6 ± 7.5 81.2 ± 3.2 12.8 ± 3.8 HLA-DR 17.4 ± 2.4 19.9 ± 2.2 13.9 ± 4.4 14.4 ± 2.5 16.7 ± 2.8 13.2 ± 4.5 Notes: TC – tumor cells, PBL — peripheral blood lymphocytes, LAK – IL-2 activated lymphocytes. The study of antitumor action of PBL from the patients with melanoma has demonstrated that the highest effect was observed against tumor cells ex- pressing the highest level of MHC of class І antigens (Table 2). Table 2. Expression of MHC class І and ІІ by lymphocytes and tumor cells of patients with melanoma Markers Antitumor activity (% cells) + – PBL TC PBL TC HLA-ABC 75.2 ± 1.3 23.8 ± 2.2 85.3 ± 2.1 15.2 ± 2.1 HLA-DR 23.0 ± 2.7 10.6 ± 4.2 13.5 ± 3.3 12.3 ± 3.7 Notes: TC – tumor cells, PBL — peripheral blood lymphocytes. So, one may conclude that the most marked anti- tumor action of lymphocytes of the patients with soft tissue sarcoma or melanoma is achieved against tumor cells expressing MHC class І antigens. Next, we have studied the expression of CD25, CD54, CD71, Ki-67 on tumor cells of various types (different soft tissue sarcoma, melanoma) and on non-acticvated and activated lymphocytes. First of all, we have revealed that expression of the markers on tumor cells and lymphocytes is characterized by pronounced individual patterns. The data have demonstrated the absence of cor- relation between the level of antitumor activity and expression of mentioned proteins (Table 3) that may be possibly explained by different tumor types studied (fibrosarcoma, rhabdomyosarcoma, liposarcoma etc). It is known that expression of the markers may differ even between the cell lines originated from the same tumor [18]. Experimental Oncology 28, 231–234, 2006 (September) 233 Table 3. Expression of CD25, CD54, CD71, Ki-67 by activated (LAK) and not ac- tivated (PBL) lymphocytes and tumor cells of patients with soft tissue sarcoma Mar- kers (% cells) Antitumor activity + – PBL LAC TC PBL LAC TC CD25 9.1 ± 1.7 15.6 ± 2.9 12.6 ± 2.4 14.4 ± 2.6 21.6 ± 3.7 8.6 ± 2.7 CD54 6.8 ± 0.9 6.5 ± 1.2 18.3 ± 7.8 7.2 ± 1.6 7.6 ± 1.3 11.3 ± 1.1 CD71 5.6 ± 0.7 6.7 ± 1.6 27.6 ± 2.6 7.4 ± 0.7 10 ± 1.6 31.5 ± 3.7 Ki-67 12.5 ± 5.4 22.3 ± 11.8 29.3 ± 8.5 12.4 ± 1.9 17.4 ± 4.5 23.3 ± 3.3 Notes: TC – tumor cells, PBL — peripheral blood lymphocytes, LAK – IL-2 activated lymphocytes. The study of expression patterns of CD25, CD54, PCNA by melanoma cells and CD25, CD56, CD11b by lymphocytes has shown that the highest antitumor action of lymphocytes is associated with the highest expression of CD11b. In some cases upon the absence of antitumor activity, the tendency for elevated CD25 expression on tumor cells has been observed (Table 4). These data point on importance of CD11b expression in realization of antitumor action of lymphocytes. Table 4. Antitumor action of tumor cells and peripheral blood lymphocytes of patients with melanoma Antitumor action (AA) Tumor cells, % cells PBL, % cells PCNA CD25 CD54 CD25 CD56 CD11b Possessing AA 19.7 ± 4.8 12.4 ± 3.9 25.5 ± 10.8 9.5 ± 1.4 10.6 ± 2.1 18.5 ± 3.4* Not possessing AA 16.9 ± 4.6 15.0 ± 2.9 33.4 ± 8.7 8.1 ± 2.4 8.8 ± 1.4 8.4 ± 1.2* Notes: *the difference between indexes for the patients of I and II groups is statistically significant (р < 0.05). Analyzing the obtained results, one may conclude that for antitumor action of PBL and LAK toward sar- coma and melanoma cells, expression of MHC class I antigens is required not only on lymphocytes, but also on tumor cells. So, one may suppose that in theses cases the central role for antitumor action belongs for cytotoxic T-lymphocytes that react on tumor antigens presented by MHC class I antigens [19, 20]. Such state- ment is in agreement with the data of literature eviden- cing that altered expression of class I HLA molecules on cells leads to significantly decreased recognition of them by CTL [21]. It’s interesting to note also that certain epitopes of HLA-А expressed on tumor cells of different genesis are making them more sensitive for immunotherapy [22]. The obtained results are evidencing that PBL and LAK of the patients with soft tissue sarcoma and melanoma are showing the highest antitumor activity toward tumor cells with elevated expression level of MHC class I antigens. Expression levels of CD25, CD71, Ki-67, CD54, CD56, CD11b, PCNA (detected by MoAb IPO-38) are characterized by significant individual variations that are possibly caused by disregulation of their expression on the level of genome. Along with the absence of statistically significant correlation between expression of different markers and antitumor action of lymphocytes and LAK toward sarcoma cells, the strict correlation between CD11b expression on lymphocytes of patients with melanoma and their antitumor action has been revealed. According to our data, the respective expression level of MHC class I antigens is promoting the sensitivity of tumor cells to action of LAK. Acknowledgement The work was supported by the Programme of Na- tional Academy of Sciences of Ukraine «Peculiarities of functioning of oncogenome» (№ 0102U003228). reFerences 1. Zinkernagel RM, Doherty PC. MHC-restricted cyto- toxic T cells: studies on the biological role of polymorphic major transplantation antigens determining T-cell restric- tion — specificity, function, and responsiveness. Adv Immunol 1979; 27: 51–177. 2. Zinkernagel RM, Hengartner H. Regulation of the im- mune response by antigen. Science 2001; 293: 251–3. 3. 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ПротивооПухолевое действие лимфокинактивированных лимфоцитов больных саркомами мягких тканей и меланомой в зависимости от эксПрессии антигенов І и ІІ класса главного комПлекса гистосовместимости Цель: изучить экспрессию антигенов І и ІІ класса главного комплекса гистосовместимости (ГКГ) на лимфоцитах и опухолевых клетках (саркомы мягких тканей и меланома кожи) и противоопухолевое действие лимфоцитов, активированных и неактивированных ИЛ-2 параллельно с экспрессией некоторых рецепторов, характеризующих протеом. Материалы и методы: культивирование эксплантатов опухоли и аутологичных лимфоцитов в диффузионных камерах с дальнейшим изучением противоопухолевого действия лимфоцитов на основании морфологических особенностей роста эксплантатов. Экспрессию антигенов CD25, CD71, Ki-67, CD54, CD56, CD11b, ядерного антигена пролиферирующих клеток (ИПО-38) определяли методом непрямой флуоресценции с помощью соответствующих моноклональных антител. Результаты: наиболее выраженное противоопухолевое действие лимфоцитов как больных саркомами мягких тканей, так и меланомой проявляется по отношению к тем опухолевым клеткам, которые экспрессируют антигены I класса ГКГ. Установлено, что значение экспрессии указанных структур для противоопухолевого действия зависит от биологических особенностей опухоли: зависимости между уровнем противоопухолевой активности и экспрессией изученных рецепторов клетками больных саркомой не выявлено. В то же время наиболее выраженное противоопухолевое действие лимфоцитов больных меланомой сочеталось с высоким уровнем экспрессии ими CD11b. Выводы: установлена прямая зависимость чувствительности опухолевых клеток к действию лимфокинактивированных клеток от уровня экспрессии антигенов ГКГ I класса на клетках как меланомы, так и сарком. Ключевые слова: антигены І и ІІ классов ГКГ, ЛАК, саркоми мягких тканей, меланома. Copyright © Experimental Oncology, 2006