LYMPHOCYTE PHENOTYPE IN PATIENTS WITH SKIN MELANOMA AFTER IMMUNOTHERAPY OF ACTIVATED LYMPHOCYTES
https://doi.org/10.15789/1563-0625-2014-6-567-576
Abstract
The major medical problem in the treatment of skin melanoma is improvement methods of treatment, increasing their effectiveness and safety. In this study, adoptive immunotherapy, using lymphocytes activated in vitro, was performed in 15 patients with metastatic melanoma. Evaluated the phenotype of peripheral blood lymphocytes and activation markers (HLA-DR, CD25, CD314, CD38, CD69) before and 3-4 weeks after immunotherapy. It is shown that for these patients is characterized by increasing the number of CD25+ and Treg lymphocytes in the bloodstream, which has not changed after immunotherapy. Adoptive immunotherapy in combination with chemotherapy resulted in a decrease of absolute number of lymphocyte, B- and T-lymphocytes, T helper cells, NKT-cells, CD314+ lymphocytes, CD38+ lymphocytes and immature T-lymphocytes (CD3+CD38+) (р < 0,05). However, there was a positive dynamic to increase the percentage of NK-cells to 32% and CD69+NK-cells to 21% and significant increase in expression of HLA-DR on all lymphocytes (p < 0.05). Adoptive immunotherapy characterized by the absence of side effects and can be recommended as accompanying to basic radiation and chemotherapy.
About the Authors
E. V. Abakushina
Medical Radiological Research Center of the Ministry of Health of the Russian Federation, Obninsk, Russian Federation 249036, Russian Federation, Kaluga Region, Obninsk, Koroleva str ., 4. Phone: 7 (484) 392-96-04. Fax: 7 (495) 956-14-40
Russian Federation
Russian Federation
PhD (Medicine), Senior Research Associate, Laboratory of Clinical Immunology, Medical Radiological Research Center of the Ministry of Health of the Russian Federation, Obninsk, Russian Federation
Yu. V. Marizina
Medical Radiological Research Center of the Ministry of Health of the Russian Federation, Obninsk, Russian Federation
Russian Federation
Russian Federation
Laboratory Research Assistant, Science Organization Department, Medical Radiological Research Center of the Ministry of Health of the Russian Federation, Obninsk, Russian Federation
G. S. Neprina
Medical Radiological Research Center of the Ministry of Health of the Russian Federation, Obninsk, Russian Federation
Russian Federation
Russian Federation
PhD (Medicine), Leading Research Associate, Laboratory of Clinical Immunology, Medical Radiological Research Center of the Ministry of Health of the Russian Federation, Obninsk, Russian Federation
D. V. Kudryavtsev
Medical Radiological Research Center of the Ministry of Health of the Russian Federation, Obninsk, Russian Federation
Russian Federation
Russian Federation
PhD, MD (Medicine), Leading Research Associate, Department of Remote Radiation Therapy, Medical Radiological Research Center of the Ministry of Health of the Russian Federation, Obninsk, Russian Federation
G. T. Kudryavtseva
Medical Radiological Research Center of the Ministry of Health of the Russian Federation, Obninsk, Russian Federation
Russian Federation
Russian Federation
PhD, MD (Medicine), Professor, Head, Radiology Department with a GroupT treatment of Bone Tumors, Medical Radiological Research Center of the Ministry of Health of the Russian Federation, Obninsk, Russian Federation
N. V. Selivanova
Medical Radiological Research Center of the Ministry of Health of the Russian Federation, Obninsk, Russian Federation
Russian Federation
Russian Federation
Research Associate, Radiology Department with a Group Treatment of Bone Tumors, Medical Radiological Research Center of the Ministry of Health of the Russian Federation, Obninsk, Russian Federation
References
1. Абакушина Е.В., Кузьмина Е.Г., Коваленко Е.И. Основные свойства и функции NK-клеток человека // Иммунология, 2012. № 4. C. 220-224. [Abakushina E.V., Kuzmina E.G., Kovalenko E.I. The main characteristics of human natural killer cells. Immunologiya = Immunology, 2012, no. 4, pp. 220-224. (In Russ.)]
2. Закурдяева И.Г., Цыб А.Ф. Диссеминированная меланома кожи (обзор литературы) // Сибирский онкологический журнал, 2011. Т. 43, №1. C. 70-76. [Zkurdyaeva I.G., Tsyb A.F. Disseminated skin melanoma (review). Sibirskiy onkologicheskiy zhurnal = Siberian Journal of Oncology, 2011, Vol. 43, no. 1, pp. 70-76. (In Russ.)]
3. Злокачественные новообразования в России в 2010 году (заболеваемость и смертность) // Под редакцией В.И. Чиссова, В.В. Старинского, Г.В. Петровой. М.: ФГБУ «МНИОИ им. П.А. Герцена» Минздравсоцразвития России, 2012. 260 c. [Malignancies in Russia in 2010 (morbidity and mortality). Eds.: Chissov V.I., Starinsky V.V., Petrova G.V]. Moscow, FGBU «MNIOI after P. A. Hertzen» of the Ministry of Health of the Russian Federation, 2012. 260 p.
4. Исмаил-заде Р.С., Белевцев М.В., Потапнев М.П., Савицкий В.П., Жаврид Э.А., Буглова С.Е. Иммуномодулирующее действие препаратов ИЛ-2 и ИФН-α в комбинации с сеансами общей гипертермии на этапах интенсивной химиотерапии у детей с далеко зашедшими злокачественными новообразованиями // Медицинская иммунология. 2006. Т. 8, № 4. С. 561-566. [Ismail-zade R.S., Belevtsev M.V., Potapnev M.P., Savitskiy V.P., Zhavrid E.A., Buglova S.E. IL-2 and IFN-alpha induced changes of peripheral blood lymphocyte subpopulations in children with advanced malignancies, treated with chemotherapy and whole body hyperthermia. Meditsinskaya immunologiya = Medical Immunology, 2006, Vol. 8, no. 4, pp. 561-566. (In Russ.)]
5. Киселевский М.В. Адоптивная иммунотерапия при злокачественных новообразованиях // Вестник Российской академии наук, 2003. №1. С. 40-44. [Kiselevskiy M.V. Adoptive immunotherapy for malignant tumors. Vestnik Rossiyskoy akademii nauk = Bulletin of the Russian Academy of Sciences, 2003, no. 1, pp. 40-44. (In Russ.)]
6. Козлов В.А., Черных Е.Р. Современные проблемы иммунотерапии в онкологии // Бюллетень СО РАМН, 2004. Т. 112, № 2. С. 13-19. [Kozlov V.A., Chernykh E.R. Modern problems of cancer immunotherapy. Byulleten` SO RAMN= Bulletin SD RAMS, Vol. 112, no. 2, 2004, pp. 13-19. (In Russ.)]
7. Кудрявцев Д.В., Мардынский Ю.С., Двинских Н.Ю., Кудрявцева Г.Т. Экспрессия Fas-рецептора (Fas) и Fas-лиганда (FasL) клетками первичной меланомы, влияние на формирование лимфоидной инфильтрации ложа опухоли и отдаленные результаты лечения // Вопросы онкологии, 2008. Т. 54, № 5. С. 582-587. [Kudryavtsev D.V., Mardynsky Yu.S., Dvinskikh N.Yu., Kudryavtseva G.T. Relationships of Fas-receptor and Fas-ligand expression by cells of primary melanoma, effect on lymphoid infiltration through tumor bed and end results. Voprosy onkologii = Problems in Oncology, 2004, Vol. 54, no. 5, pp. 582-587. (In Russ.)]
8. Кудрявцев Д.В., Абакушина Е.В., Неприна Г.С., Кудрявцева Г.Т., Селиванова Н.В. Опыт применения терапии лимфокин-активированными киллерами (ЛАК) в лечении метастатической меланомы кожи // Злокачественные опухоли, 2013. Т. 6, № 2. C 142. [Kudryavtsev D.V., Abakushina E.V., Neprina G.S., Kudryavtseva G.T., Selivanova N.V. Experience of using lymphokine activated killer cells (LAK) therapy in the treatment of metastatic melanoma. Zlokachestvennye opukholi = Malignant Tumors, 2013, Vol. 6, no. 2, p. 142. (In Russ.)]
9. Литвинова Л.С., Гуцол А.А., Сохоневич Н.А., Кофанова К.А., Хазиахматова О.Г., Шуплецова В.В., Кайгородова Е.В., Гончаров А.Г. Основные поверхностные маркеры функциональной активности Т-лимфоцитов // Медицинская иммунология, 2014. Т. 16, № 1. С. 7-26. [Litvinova L.S., Gutsol A.A., Sokhonevich N.A., Kofanova K.A., Khaziakhmatova O.G., Shupletsova V.V., Kaigorodova E.V., Goncharov A.G. Basic surface markers of functional activity T-lymphocytes. Meditsinskaya immunologiya = Medical Immunology, 2014, Vol. 16, no. 1, pp. 7-26. (In Russ.)]
10. Маризина Ю.В., Неприна Г.С., Кудрявцев Д.В., Селиванова Н.В., Абакушина Е.В. Фенотип лимфоцитов у больных меланомой после иммунотерапии // Российский биотерапевтический журнал, 2014. T. 13, № 1. С. 109. [Marizina Yu.V., Neprina G.S., Kudryavtsev D.V., Selivanova N.V., Abakushina E.V. Phenotype of lymphocytes in patients with melanoma after immunotherapy. Rossiyskiy bioterapevticheskiy zhurnal = Russian Journal of Biotherapy, 2014, Vol. 13, no. 1, p. 109. (In Russ.)]
11. Нехаева Т.Л. Оптимизация аутологичных дендритно-клеточных вакцин для лечения больных злокачественными новообразованиями // Сибирский онкологический журнал, 2013. T. 57, № 3. С. 52-56. [Nekhayeva T.L. Autologous dendritic cell vaccine optimization for therapy of patients with disseminated malignant neoplasms. Sibirskiy onkologicheskiy zhurnal = Siberian Journal of Oncology, 2013, Vol. 57, no. 3, pp. 52-56. (In Russ.)]
12. Смирнова А.В., Лукашина М.И., Михайлова И.Н., Демидов Л.В., Огородникова Е.В., Вишнякова Л.Ю., Никитин К.Д., Барышников А.Ю. Исследование роли экспрессии молекул HLA-I и HLA-II классов в активации лимфоцитов // Российский биотерапевтический журнал, 2006. Т.5, № 4.
13. С. 8-14. [Smirnova A.V., Lukashina M.I., Mikhailova I.N., Demidov L.V., Ogorodnikova E.V., Vishnyakova L.Yu., Nikitin K.D., Baryshnikov A.Yu. Role of HLA-I and HLA-II class molecules in lymphocyte activation. Rossiyskiy bioterapevticheskiy zhurnal = Russian Journal of Biotherapy, 2006, Vol. 5, no. 4, pp. 8-14. (In Russ.)]
14. Титов К.С., Киселевский М.В., Демидов Л.В., Сельчук В.Ю., Грицай А.Н., Кучмезов Э.Х. Внутрибрюшинная биотерапия с использованием ИЛ-2 и донорских ЛАК-клеток при метастатических асцитах у больных раком яичников // Российский биотерапевтический журнал, 2011. Т. 10, № 2. С. 51-54. [Titov K.S., Kiselevskiy M.V., Demidov L.V., Selchuk V.Yu., Gritsay A.N., Kuchmezov E.K. Intraperitoneal IL-2 and allogen lymphokine activated killers biotherapy of malignant peritoneal effusions in ovarian cancer patients. Rossiyskiy bioterapevticheskiy zhurnal = Russian Journal of Biotherapy, 2011, Vol. 10, no. 2, pp. 51-54. (In Russ.)]
15. Хайдуков С.В., Зурочка А.В., Тотолян Арег А., Черешнев В.А. Основные и малые популяции лимфо-цитов периферической крови человека и их нормативные значения (методом многоцветного цитометрического анализа) // Медицинская Иммунология, 2009. Т. 11, № 2-3. С. 227-238. [Khaidukov S.V., Zurochka A.V., Totolian Areg A., Chereshnev V.A. Major and lymphocyte populations of human peripheral blood lymphocytes and their reference values, as assayed by multi-colour cytometry. Meditsinskaya Immunologiya = Medical Immunology, 2009, Vol. 11, no. 2-3, pp. 227-238. (In Russ.)]
16. Cheng M., Chen Y., Xiao W., Sun R., Tian Z. NK cell-based immunotherapy for malignant diseases. Cell Mol. Immunol., 2013, Vol. 3, no. 10, рp. 1-23.
17. Clausen J., Vergeiner B., Enk M., Petzer A.L., Gastl G., Gunsilius E. Functional significance of the activation-associated receptor CD25 and CD69 on human NK-cells and NK-like T-cells. Immunobiology, 2003, Vol. 207, no. 2, pp. 85-93.
18. Ives N.J., Stowe R.L., Lorigan P., Wheatley K. Chemotherapy compared with biochemotherapy for the treatment of metastatic melanoma: a meta-analysis of 18 trials involving 2,621 Patients. J. Clin. Оncol, 2007, Vol. 25, no. 34, pp. 5426-5434.
19. Sandoval-Montes C., Santos-Argumedo L. CD38 is expressed selectively during the activation of a subset of mature T-cells with redused proliferation but improved potential to produce cytokines. Leukocyte Biol., 2005, Vol. 77, pp. 513-521.
20. Sangiolo D., Martinuzzi E., Todorovic M., Vitaggio K., Vallario A., Jordaney N., Carnevale-Schianca F., Capaldi A., Geuna M., Casorzo L., Nash R., Aglietta M., Cignetti A. Alloreactivity and anti-tumor activity segregate within two distinct subsets of cytokine-induced killer (CIK) cells: implications for their infusion across major HLA barriers. Int. Immunol., 2008, Vol. 20, no. 7, pp. 841-848.
21. Terunuma H., Deng Х., Nishino N., Watanabe K. NK cells-based autologous immune enhancement therapy for cancer. JSRM, 2013, Vol. 9, no.1, pp. 9-13.
22. van der Vliet H.J., Balk S.P., Exley M.A. Natural Killer T Cell–Based Cancer Immunotherapy. J. Clin. Cancer. Res., 2006, Vol. 12, no. 20, pp. 5921-5923.
23. Whitaker D.K., Sinclair W. Melanoma Advisory Board. Guideline on the management of melanoma. J. S. Afr. Med., 2004, Vol. 94, no. 8, pp. 699-707.
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For citations:
Abakushina E.V., Marizina Yu.V., Neprina G.S., Kudryavtsev D.V., Kudryavtseva G.T., Selivanova N.V. LYMPHOCYTE PHENOTYPE IN PATIENTS WITH SKIN MELANOMA AFTER IMMUNOTHERAPY OF ACTIVATED LYMPHOCYTES. Medical Immunology (Russia). 2014;16(6):567-576. (In Russ.) https://doi.org/10.15789/1563-0625-2014-6-567-576
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