Иммунофенотипические и морфо-функциональные особенности активированных лимфоцитов тема диссертации и автореферата по ВАК РФ 14.00.36, кандидат биологических наук Карамзин, Андрей Михайлович

  • Карамзин, Андрей Михайлович
  • кандидат биологических науккандидат биологических наук
  • 2008, Москва
  • Специальность ВАК РФ14.00.36
  • Количество страниц 108
Карамзин, Андрей Михайлович. Иммунофенотипические и морфо-функциональные особенности активированных лимфоцитов: дис. кандидат биологических наук: 14.00.36 - Аллергология и иммулология. Москва. 2008. 108 с.

Оглавление диссертации кандидат биологических наук Карамзин, Андрей Михайлович

Введение.

1.Обзор литературы.

2.Материалы и методы.

3. Результаты исследования.

I I г

3.1 Морфо-функциональная и иммунофенотипическая характеристика лимфокин активированных киллеров, генерированных из мононуклеарных лейкоцитов периферической крови доноров.

3.1.1 Морфологическая характеристика мононуклеарных лейкоцитов периферической крови доноров при активации ИЛ-2.

3.1.2 НК-активность лимфокин активированных киллеров.

3.1.3 Цитотоксическая активность лимфокин активированных киллеров по отношению к опухолевым и ^трансформированным линиям различного гистогенеза.

3.20ценка иммунофенотипа лимфокин активированных киллеров, генерированных из мононуклеарных лейкоцитов периферической крови доноров.

З.ЗКомбинированное действие ЛАК и цисплантина на клетки немелкоклеточного рака легкого.

3.4 Генерация ЛАК из МЛ селезенки и опухолевого экссудата онкологических больных.

3.4.1 Получение лимфокин активированных киллеров из лимфоцитов селезенки онкологических больных.

3.4.2 Генерация лимфокин активированных киллеров из мононуклеарных лейкоцитов опухолевых выпотов.

3.5 Цитотоксическая активность МНК при воздействии иммуномодуляторов различной природы.

Обсуждение результатов.

Выводы.

Рекомендованный список диссертаций по специальности «Аллергология и иммулология», 14.00.36 шифр ВАК

Заключение диссертации по теме «Аллергология и иммулология», Карамзин, Андрей Михайлович

Выводы

1.Оптимальным сроком для генерации ЛАК является 3-5 сут., в этот период появляются активированные формы типа иммунобластов и пролимфоцитов. Последующее культивирование приводит к увеличению содержания в культурах МЛ клеток макрофагального ряда.

2. Установлено, что лимфокин-активированные лимфоциты характеризуются более высокой пролиферативной и НК-активностыо, и отличаются высоким уровнем экспрессии молекул адгезии (CD58), активационных антигенов (CD38, CD25) и маркеров НК (CD16, CD56).

3. МНК и ЛАК обладают избирательной цитотоксической активностью по отношению к опухолевым клеточным линиям различного генеза и практически не оказывают цитопатогенного действия на нетрасформированные клетки.

4. ЛАК способны эффективно лизировать клетки немелкоклеточного рака легкого, устойчивые к действию препаратов платины.

5. ЛАК, полученные из мононуклеарных лейкоцитов селезенки и злокачественных выпотов онкологических больных, характеризуются высоким содержанием НК и обладают способностью эффективно лизировать аллогенные и аутологичные опухолевые клетки.

6. Показано, что иммуномодуляторы различной, в том числе и нецитокиновой природы, достоверно повышают спонтанную НК- активность и цитотокчиность лимфоцитов по отношению к опухолевым клеткам.

Список литературы диссертационного исследования кандидат биологических наук Карамзин, Андрей Михайлович, 2008 год

1. Гуторов C.JI. Гемицитабин и пеметрексед в химиотерапии немелкоклеточного рака легкого.//Российский медицинский журнал. 2006.-т.14.-с. 1032-1035

2. Давыдов М.И., Нормантович В.А., Полоцкий Б.Е., Киселевский М.В., Волков С.М. Иммунотерапия «интерлейкин-2/JIAK» в лечении больных злокачественным плевральным выпотом. «Опыт 10 наблюдений». //Вестник Моск. Онкол. Общ. 1998: № 9, с.З.

3. Давыдов М. И., Нормантович В. А., Киселевский М. В., Волков С. М. и др. Адоптивная иммунотерапия при опухолевых плевритах: клиниколабораторное исследование // Российский онкологический журнал. 2000, № 6. с. 14-17.

4. Давыдов М.И., Киселевский М.В., Полоцкий Б.Е. Адоптивная иммунотерапия опухолевых плевритов.// Здравоохранение Туркменистана.-2000.-№ З.-с. 4-7.

5. Давыдов М.И., Оразгельдыев K.P., С.М.Волков, Тугуз А.Р., Казанова Г.В., Киселевский М.В. Адоптивная иммунотерапия опухолевых плевритов. Новое в онкологии: Сб. научных трудов. Выпуск 5.-2001.- С. 72-88.

6. Киселевский М. В., Блюменберг А. Г. Адоптивная иммунотерапия рака яичников // Сборник статей, приуроченный к Европейской школе по онкологии. 2001. С. 164-176.

7. Киселевский М.В.,. Казанова Г.В. Варфоломеева С.Р., Добреньков К.В., Тимаков A.M. Опыт применения интерлейкина-2 и лимфокинактивированных клеток-киллеров в терапии онкогематологических заболеваний у детей.// Иммунология. 2002 .-№ 1.- С. 56 — 59.

8. Киселевский М.В., Титов К.С., Тер-Ованесов М.Д. Перспективы адоптивной иммунотерапии радикально оперированного рака желудка. //Российский биотерапевтический журнал. -2002. -№ 4.-С.46-48.

9. Малахова Н.В., Фигурин K.M., Киселевский М.В., Быковская С.Н.

10. Динамика цитотоксичности мононуклеаров крови у больных, раком мочевого пузыря: при эндолимфатической иммунотерапии лимфокинактивированными киллерами и рекомбинантным ИЛ-2.// Бюлл. Экспер. Биол. Мед. -1996.-№2 С.188-191.

11. Нормантович В.А., Давыдов М.И., Полоцкий Б.Е., Киселевский М.В. Лимфохимо-ЛАК-терапия рака легкого.// 6 Национальный, конгресс по болезням органов дыхания; Новосибирск .1996.-G. 462.

12. Оразгельдыев К.Р." Внутриплевральная иммунотерапия опухолевых плевритов // Диссертация на соискание ученой степени кандидата! медицинских наук. РОНЦ РАМН им. Блохина, Москва, 2001- г.

13. Шубина И.Ж., Блюменберг А.Г., Волков С.М. и др. Адоптивная иммунотерапия злокачественных новообразований . 2007.-№Г1.С.9-15.

14. Acha-Orbea Н, Groscurth Р, Lang R, Stitz L, Hengartner Hv Characterization of cloned? cytotoxic lymphocytes with NK-like activity. Jour Immunol. 1983;130:2952-2959.

15. Aglietta M, Bertolini F, Carlo-Stella G, et al. Ex-vivo expansion of: hematopoietic cells and their clinical use.// Haematologica. 1998; 83:824-48.

16. Allavena P, Paganin C, Zhou D, Bianchi G, Sozzani S, Mantovani A. Interleukin-12 is chemotactic for natural killer cells and stimulates their interaction with vascular endothelium. Blood. 1994;84:2261-2268.

17. Anita S, Chong F, Scuderi P, Grimes WJ!, Hersh EM: Tumor targets stimulate IL-2 activated killer cells to produce Interferon-gamma and tumor necrosis factor. J Immunol. 1989;142:2133-2139.

18. Arcese W, Aversa F, Bandini G, et al Clinical use of allogeneic hematopoietic stem cells from sources other than bone marrow. Haematologica. 1998; 83 :159-82.

19. Barlozzari T, Reynolds CW, Herberman RB. In vivo role of natural killer cells: involvement of large granular lymphocytes in the clearance of tumor cells in anti-asialo GMl-treated rats. J Immunol. 1983; 131: 1024-1027.

20. Barlozzari T, Reynolds CW, Herberman RB. Inhibition of pluripotent hematopoietic stem cells of bone marrow by large granular lymphocytes. Proc Natl Acad Sci USA. 1987;84(21):7691-5.

21. Barlozzari T, Leonhardt J, Wiltrout RH, Herberman RB, Reynolds CW. Direct, evidence for the role of LGL in the inhibition of experimental tumor metastases. J Immunol. 1985; 134: 2783-2789.

22. Bear HD. Tumor-specific suppressor T-cells which inhibit the in vitro generation of cytolytic T-cells from immune and early tumor-bearing host spleens//Cancer Res. -1986:-vol.46(4 Pt l).-p.l805-1812

23. Bendall LJ, Kortlepel K, Gottlieb DJ. GM-CSF enhances IL-2-activated natural, killer cell lysis of clonogenic AML cells by upregulating target cell expression of ICAM-1. Leukemia. 1995;9:677-684.

24. Bernsen M.R., Van der Velden A.W., Everse L.A. et al. Interleukin-2: hope in cases of cisplain-resistant tumours /Cancer immunol. Immunother.— 1998.— Vol. 46.—P. 41-47.

25. Bertolini F, de Vincentiis A, Lanata L, et al. Allogeneic hematopoietic stem cells from sources other than bone marrow: biological and technical aspects. Haematologica. 1997; 82:220-38.

26. Bindon J., Ruell P. et al. // J. Immunol. 1984.— Vol. 3.— P. 475-478.

27. Boon T, DePlaen E, Traversari C, et al. Identification of tumor rejection antigens recognized by T lymphocytes. Cancer Surv.1992; 13:23-37.

28. Braud VM, Allan DS, O'Callaghan CA, et al HLA-E inds to natural killer cell receptors CD94/NKG2A, B band C. Nature. 1998; 391; 795-9.

29. Brinkmann OA, Bruns F, Prott F-J, Hertie L. Possible synergy of radiotherapy and chemo-immunotherapy in metastatic renal cell carcinoma. Anticancer Res. 1999;19:1583-1588.

30. Van den Broek ME, Kägi D, Ossendorp F, Toes R, Vamvakas S, Lutz WK, et al. Decreased tumor surveillance in perforin-deficient mice. J Exp Med. 1996; 184: 1781-1790.

31. Van der Brüggen P, Traversari C, Chomez P, et al. Agene encoding an antigen recognized by cytolytic T lymphocytes on human melanoma. Science. 1991;254:1643-7.

32. Campiglio M, Somenzi G, Ogliati C et al. Role of proliferation in Her2 status predicted response to doxorubicin. Int J Cancer. 2003; 105 (4): 568-73.

33. Chang JCN, Wooten EC, Tsimelzon A et al. Gene expression patterns for de novo and acquired docetaxel resistance in patients with locally advanced breast cancer. Proc Am Soc Oncol. 2003; 22: 9 (abstr. 32).

34. Chen R, Pan L, Zhou S. Cytotoxicities of low dose anticancer agents combining lymphokine activated killer cell against ovarian adenocarcinoma cell line SKOV3. ZhonghuaFu ChanKe ZaZhi. -1999.-vol. 34(3).-p.l72-174.

35. Ciccone E, Grossi CE, Velardi A. Opposing functions of activatory T-cell receptors and inhibitory NK-cell receptors on cytotoxic T cells. Immunol Today. 1996;17:451-3.

36. Colonna M. Immunology: unmasking the killer's accomplice. Nature. 1998; 391:642-3.

37. Cretney E, Takeda K, Yagita H, Glaccum M, Peschon JJ, Smyth MJ. Increased susceptibility to tumor initiation and metastasis in TNF-related apoptosis-inducing ligand-deficient mice. J Immunol. 2002; 168: 1356-1361.

38. Czop JK, Kay J. Isolation and characterization of beta-glucan receptors on human mononuclear phagocytes. J Exp Med. 1991;173:1511—1520.

39. Daniels B, Karlhofer FM, Seaman WE, Yokoyama WM. A natural killer cell receptor specific for a major histocompatibility complex class I molecule. J. Exp Med. 1994; 180:687-92.

40. Deblaker-Hohe DF, Yamauchi A, Yu CR, Horvath-Arcidiacono JA, Bloom ET. IL-12 synergizes with IL-2 to induce Lymphokine-activated cytotoxicity and perforin and granzyme gene expression in fresh human NK cells. Cell Immunol. 1995;165:33-43.

41. Dighe AS, Richards E, Old LJ, Schreiber RD. Enhanced in vivo growth and resistance to rejection of tumor cells expressing dominant negative IFN '/receptors. Immunity. 1994; 1:447-456.

42. Donaldson K.L., Goolsby G.L., WahlA.F. Cytotoxicity of the anticancer agents cisplatin and taxol during cell proliferation and cell cycle/ Int.J.Cancer.-1994.-vol.57.-p.847-855.

43. Donohue JH, Rosenstein M, Chang AE, Lotze MT, Robb RJ, Rosenberg SA. The systemic administration of purified interleukin 2 enhances the ability ofsensitized murine lymphocytes to cure a disseminated syngeneic lymphoma. J Immunol. 1984.132(4):2123—2128.

44. Dunne J, Lynch S, O'Farrelly C, Todryk S, Hegarty JE, Feighery C, Doherty DG. Selective expansion and partial activation of human NK cells and NK receptor-positive T cells by IL-2 and IL-15. J Immunol. 2001;167:3129-3138.

45. Eisenthal A, Lafreniere R, Lefor AT, Rosenberg SA. Effect of anti-B16 melanoma monoclonal antibody on established murine B16 melanoma liver metastases. Cancer Res. 1987.47(11):2771-2776.

46. Ettinghausen SE, Lipford EH 3rd, Mulé JJ, Rosenberg SA. Systemic administration of recombinant interleukin 2 stimulates in vivo lymphoid cell proliferation in tissues. J Immunol. 1985.135(2):1488-1497.

47. Ettinghausen SE, Lipford EH 3rd, Mulé J J, Rosenberg SA. Recombinant interleukin 2 stimulates in vivo proliferation of adoptively transferred lymphokine-activated killer (LAK) cells. J Immunol. 1985.135(5):3623-3635.

48. Eremin 0,- Ashby J, Stephens JP. Human natural cytotoxicity in the blood and. lymphoid organs of healthy donors and patients with malignant disease. Int J? Cancer. 1978; 21:35-41.

49. Falk C. S., Noessner E., Weiss E. H., Schendel D. J. Retaliation against tumor cells shoing aberrnt HLA expression using lymphokine activated killer-derived T cells.— Cancer Res. 2002, vol. 62. p. 480-487.

50. Fischer DG, Pide MC, Koren HS, Snyderman R. Chemotactically responsive and nonresponsive forms of a continuous human monocyte cell line. J Immunol. 1980;125:463-465.

51. Freedman R.S. Immunotherapy for peritonei ovarian carcinoma metastasis using ex vivo expanded tumorinfiltrating lymphocytes / R.S. Freedman, C.D. Platsoncas // 1996.—Vol. 82.—P. 115-116.

52. Gautan S.C., Chikkala N.F., Lewis I., Grabowski D,R., Finke J.H., Ganapathi R. Therapeutic efficacy of interleukin-2 activated killer cells against adriamycin' resistant mouse B-16-BL6 melanoma.// Anticancer Res.- 1992.-vol.12.-p.921-925

53. Gong YH, Guo X, Zhang XQ. Immunoelectron microscopic studies on the process of tumor cytolysis mediated by lymphokine activated NK cells. Chung-hua-Ping-Li-Hsueh-Tsa-Chih. 1994;23:17-19.

54. Gorelik E, Wiltrout RH, Okumura K, Habu S, Herberman RB. Role of NK cells in the control of metastatic spread and growth of tumor cells in mice. Int J Cancer. 1982; 30: 107-112.

55. Gui XE, Rinaldo CRJr, Ho M. Natural killer cell activity in renal transplant recipients receiving cyclosporine. Infect Immun. 1983; 41: 965-970.

56. Guinan EC, Gribben JG, Boussiotis VA, Freeman GJ, Nadler LM. Pivotal role of the B7: CD28 pathway in transplantation tolerance and tumor immunity. Blood. 1994; 84:3261-82.

57. Hanna N and Burton RC. Definitive evidence that natural killer (NK) cells inhibit experimental tumor metastases in vivo. J Immunol. 1981; 127: 1754-1758.

58. Hanna N. Inhibition of experimental tumor metastasis by selective activation of natural killer cells. Cancer Res. 1982; 42: 1337-1342.

59. Havele C, Bleackly RC, Paetkau V. Conversion of specific to nonspecific cytotoxic T lymphocytes. Jour Immunol. 1986;137:1448-1454.

60. Herberman RB, Nunn ME, Lavrin DH. Natural cytotoxic reactivity of mouse lymphoid cells against syneneic and allogeneic tumors. I. Distribution of reactivity and specificity. Int J Cancer. 1975; 16: 216-29.

61. Herberman RB, Hiserodt J, Vujanovic N, Balch C, Lotzova E, Bolhuis R, et al. Lymphokine-activated killer cell activity. Immunol Today. 1987; 8: 178-181.

62. Hersey P, Edwards A, Honeyman M, McCarthy WH. Low natural-killer-cell activity in familial melanoma patients and their relatives. Br J Cancer. 1979; 40: 113-122.

63. Hong C, Park SH. Application of natural killer T cells in antitumor immunotherapy. Crit Rev Immunol. 2007;27(6):511-25.

64. Imai K, Matsuyama S, Miyake S, Suga K, Nakachi K. Natural cytotoxic activity of peripheral-blood lymphocytes and cancer incidence: an 11-year follow-up study of a general population. Lancet. 2000; 356: 1795-1799.

65. Inge TH, Hoover SK, Frank JL, Kawabata TT, Bethke KP, Bear HD. Enhancement of cytotoxic T lymphocyte growth from spleens of P815-tumor-bearing host mice with mafosfamide.//Cancer Immunol. Immunother. -1992.-vol.35(2).-p.l 19-126.

66. Janeway CA Jr, Bottomly K. Signals and signs for lymphocyte responses. Cell. 1994; 76:275-85.

67. Johnson BJ, McMurray DN. Cytokine gene expression by cultures of human lymphocytes with autologous Mycobacterium tuberculosis-infected monocytes. Infect Immun. 1994;63:1444-1450.

68. Kági D, Ledermann B, Bürki K, Seiler P, Odermatt B, Olsen KJ, et al. Cytotoxicity mediated by T cells and natural killer cells is greatly impaired in perforin-deficient mice. Nature. 1994; 369: 31-37.

69. Kagl D, Ledermann G, Burki K, Seller P, Oldermatt B, Olsen KJ, Podack ER, Zinkernagel WM, Hengartner H. Cytotoxicity mediated by T cells and natural killer cells is greatly impaired in perforin deficient mice. Nature. 1994;369:31-37.

70. Kammula U.S.; Marineóla F.M. Source: «Cancer Immunotherapy: Is There Real Progress at Last?» BioDrugs Volume: 11 Number: 4 Page: 249 260.

71. Kaplan DH, Shankaran V, Dighe AS, Stockert E, Aguet M, Old LJ, et al. Demonstration of an interferon 7-dependent tumor surveillance system in immunocompetent mice. Proc Natl Acad Sci USA. 1998; 95: 7556-7561.

72. Karre K, Ljunggren H-G, Piontek G, Kiessling R. Selective rejection of H2-deficient lymphoma variants suggests alternative immune defense strategy. Nature. 1986;319:675-678.

73. Kazuyoshi Takeda and Ko Okumura CAM and NK Cells. eCAM 2004 1 (1): 1727.

74. Khar A, Pardhasaradhi BV, Varalakshmi C, Ali AM, Kumari AL. Natural killer cell as the effector which mediates in vivo apoptosis in AK-5 tumor cells. Cell Immunol. 1997;177:86-92.

75. Kim KH, Lee YS, Jung IS, Park SY, Chung HY, Lee IR, Yun YS. Acidic polysaccharide from Panax ginseng, ginsan, induces Thl cell and macrophage cytokines and generates LAK cells in synergy with rIL-2. Planta Med. 1998;64:110-115.

76. Kimura H, Yamaguchi Y. Postsurgical adjuvant immunotherapy against primary non-small cell lung cancerippon Geka Gakkai Zasshi. 1998 vol. 99(5):279-84.

77. Kobari M, Egawa S, Shibuya K, Sunamura M, Saitoh K, Matsuno S. «Effect of intraportal adoptive immunotherapy on liver metastases after resection of pancreatic cancer.» Br J Surg. 2000 Jan;87(l):43-8.

78. Van Kooten C, Banchereau J. Functions of CD40 on B cells, dendritic cells and other cells. Curr Opin Immunol. 1997; 9:330-7.

79. Korkolopoulou P, Kaklamanis L, Pezzella F, Harris AL, Gatter KC. Loss of antigen-presenting molecules (MHC class I and, TAP-1) in lung cancer. Br J« Cancer. 1996; 97:148-53.

80. F. Komatsu ; T. Masuda «Cell-Cell Adhesion-Independent Killing Due to-Lymphokine Activated Killer Cells Against Glioblastoma Cell Lines» Source: Oncology Research Volume: 12 Number: 9 Page: 371 381, 2003.

81. Kjaergaard J, Marianne E et al "Biodistribution ens tumor localization of lymphokine-activated killer T cells following different routes of administstration into tumor-bearing animals." Cancer Immunol Immunother (2000) 48:550 560.

82. Kwak J-Y., Han M.K., Choi K-S., Park I-H. et al. «Cytokines Secreted by Lymphokine-Activated Killer Cells Induce Endogenous Nitric Oxide Synthesisand Apoptosis in DLD-1 Colon Cancer Cells» Source: Cellular Immunology.-2003.-vol.203.- n. 2.- p. 84 94

83. Lafreniere R, Rosenberg SA. Successful immunotherapy of murine experimental hepatic metastases with lymphokine-activated killer cells and recombinant interleukin 2. Cancer Res. 1985;45(8):3735-3741.

84. Lanier LL, Le AM, Civin CI, Loken MR, Phillips JH. The relationship of CD16(Leu-ll) and Leu-19 (NKH-1) Antigen expression on Human peripheral Blood NK cells and cytotoxic lymphocytes. Jour Immunol. 1986;136:4480-4485.

85. Liu X., Li D., Zhang C.et al. Treatment of 121 patients with malignant effusion-due to advanced lung cancer by intrapleural transfer of autologus or allogenic LAK cells combined with RIL-2/ Med. Sc. J. 1993.— Vol. 8.— P. 186-189.

86. Lotze MT, Line BR, Mathisen DJ, Rosenberg SA. The in vivo distribution of autologous human and murine lymphoid cells grown in T cell growth factor (TCGF): implications for the adoptive immunotherapy of tumors. J Immunol. 1980; 125(4): 1487-1493.

87. Lotze MT, Grimm EA, Mazumder A, Strausser JL, Rosenberg SA. Lysis of fresh and cultured autologous tumor by human lymphocytes cultured in T-cell growth factor. Cancer Res. 1981;41(11 Pt l):4420-4425.

88. Maeurer MJ, Gollin SM, Martin D, et al. Tumor escape from immune recognition. J Clin Invest 1996; 98:1633-41.1994; 84:3261-82.

89. Matsuzaki I, Suzuki H, Kitamura M, Minamiya Y, Kawai H, Ogawa J. Cisplatin induces fas expression in esophageal cancer cell lines and enhanced cytotoxicity in combination with LAK cells. Oncology.- 2000.-vol. 59(4).-p.336-343.

90. Mazumder A, Eberlein TJ, Grimm EA, Wilson DJ, Keenan AM, Aamodt R, Rosenberg SA. Phase I study of the adoptive immunotherapy of human cancer with lectin activated autologous mononuclear cells. Cancer. 1984;53(4):896-905.

91. Medawar PB. Croonian Lecture. Proc Royal Soc. B. 1958; 148:159-61.

92. Merogi AJ, Marrogi A J, Ramesh R, Robinson WR, Fermin CD, Freeman SM. Tumor-host interaction: analysis of cytokines, growth factors, and tumorinfiltrating lymphocytes in ovarian carcinomas. Hum Pathol. 1997; 28:321-31.

93. Mickel RA, Kessler DJ, Taylor JM, Lichtenstein A. Natural killer cell cytotoxicity in the peripheral bloodnodes, and tumor of head and neck cancer patients. Cancer Res. 1988; 48: 5017-5022.

94. Miller JS, Alley KA, McGlave PB. Differentiation of natural killer cells from human primitive marrow progenitors in a stroma based long term culture system: identification of a CD34+/CD7+ NK progenitor. Blood. 1994; 83:2594-601.

95. Mrozek E, Anderson P, Caligiuri MA. Role of inter leukin-15 in the development of human CD56+ natural killer cells from CD34+ hematopoietic progenitor cells. Blood. 1996; 87:2632-40.

96. Mulé JJ, Shu S, Schwarz SL, Rosenberg SA. Adoptive immunotherapy of established pulmonary metastases with LAK cells and recombinant interleukin-2. Science. 1984;225(4669): 1487-1489.

97. Mulé JJ, Shu S, Rosenberg SA. The anti-tumor efficacy of lymphokine-activated killer cells and recombinant interleukin 2 in vivo. J Immunol. 1985;135(l):646-652.

98. Murphy JB. Monography. Rockefeller Institute of Medcal Research 1926; 21:1168.

99. Nakajima T, Mizushima N, Kanai K. Relationship between natural killer activity and development of hepatocellular carcinoma in patients with cirrhosis of the liver. Jpn J Clin Oncol. 1987; 17: 327-332.

100. Nieto M, Navarro F, Perez-Villar JJ, del Pozo MA, Gonzalez-Amaro R, Mellado M, Frade JM, Martinez AC, Lopez-Botet M, Sanchez-Madrid F. Roles of chemokines and receptor polarization in NK-target cell interactions. J Immunol. 1998;161:3330-3339.

101. R Nirmala and PR Narayanan Flowcytometry A rapid tool to correlate-functional activities of human peripheral blood lymphocytes with theircorresponding phenotypes after in vitro stimulation. BMC Immunol.- 2002.-Vol.3.-p. 9-19.

102. Okumura K, Habu S, Kasai M. The role of NK cells in resistance of in vivo tumors. Adv Exp Med Biol. 1982; 155: 773-784.

103. Onrust SV, Harti PM, Rosen SD, Hanahan D. Modulation of L-selection ligand expression during an immune response accompanying tumorigenesis in transgenic mice. J Clin Invest. 1996; 97:54-64.

104. Ortaldo JR, Herberman RB. Heterogeneity of natural killer cells. Ann Rev Immunol. 1984;2:359-394.

105. Ozkan A., Ayhan A., Fiskin K. Combined effect of epirubicyn and lymphokine activated killer cells on the resistant human breast cancer carcinoma.// Cell. Biol. Toxicol.-2004.-vol.20.-p.261-271.

106. Pittet MJ, Speiser DE, Valmori D, Cerottini J, Romero P. Cytolytic Effector Function in Human Circulating CD8+ T Cells Closely Correlates with CD56 Surface Expression. J Immunol. 2000; 164:1148-1152.

107. Phillips JH, Lanier LL. Dissection of the LAK phenomenon. J Exp Med. 1986;164:814-825.

108. Rasku MA, Clem AL, Telang S, Taft B, Gettings K, Gragg H, Cramer D, Lear SC, McMasters KM, Miller DM, Chesney J. Transient T cell depletion- causes regression of melanoma metastases.Int Immunol. 2008 6(1): 12.

109. Rayner AA, Grimm EA, Lotze MT, Chu EW, Rosenberg SA. Lymphokine-activated killer (LAK) cells. Analysis of factors relevant to the immunotherapy of human cancer. Cancer.- 1985.-vol.15;55(6).-p.1327-1333.

110. Rayner AA, Grimm EA, Lotze MT, et al. Lymphokine activated killer (LAK) cell phenomenon. IV. Lysis by LAK cell clones of fresh human tumor cells from1 autologous and multiple allogeneic tumors. J Natl Cancer Inst. 1985; 75:67-75.

111. Ralph P, Moore MAS, Nillson K. Lysozyme synthesis by established human and murine histiocytic lymphoma cell lines. J Exp Med. 1976;143:1528-1533.

112. Restifo NP, Esquivel F, Kawakami Y, et al. Identification of human cancers deficient in antigen processing. J Exp Med.-1993 .-vol. 177.p-265-72.

113. Roberts K, Lotze MT, Rosenberg SA. Separation and functional studies of the human lymphokine-activated killer cell. Cancer Res. 1987;47(16):4366-4371.

114. Roder JC, Haliotis T, Klein M, Korec S, Jett JR, Ortaldo J, et al. A new immunodeficiency disorder in humans involving NK cells. Nature 1980; 284: 553555.

115. Ronald H. Goldfarb «Антиметастатическая терапия». («Биологические методы лечения онкологических заболеваний» под редакцией Т.ДеВита, С.Хеллмана, С.Розенберга. М.: Медицина 2002).

116. Rosenberg SA, Grimm EA, McGrogan M, Doyle M, Kawasaki E, Koths K, Mark DF. Biological activity of recombinant human interleukin-2 produced in Escherichia coli. Science. 1984;223(4643):1412-1414.

117. Rosenberg SA. Adoptive immunotherapy of cancer: accomplishments and prospects. Cancer Treat Rep. 1984;68(l):233-255.

118. Rosenberg SA. Immunotherapy of cancer by systemic administration of lymphoid cells plus interleukin-2. J Biol Response Mod. 1984;3(5):501-511.

119. Rosenstein M, Yron I, Kaufmann Y, Rosenberg SA. Lymphokine-activated killer cells: lysis of fresh syngeneic natural killer-resistant murine tumor cells by lymphocytes cultured in interleukin 2. Cancer Res. 1984;44(5):1946-1953.

120. Rosenberg SA, Mulé JJ, Spiess PJ, Reichert CM, Schwarz SL. Regression of established pulmonary metastases and subcutaneous tumor mediated by the systemic administration of high-dose recombinant interleukin 2. J Exp Med. 1985; 161(5): 1169-1188.

121. Rosenberg SA, Spiess P, Lafreniere R. A new approach to the adoptive immunotherapy of cancer with tumor-infiltrating lymphocytes. Science. 1986;233(4770): 1318-1321.

122. Rosenberg S.A., Lotze B., Yang J.C. et al. //Prospective randomized trial of high dose of! IL-2 alone and in conjugation with LAK for treatment of patients with advanced cancer.// J. NatLCancer Inst. 1993.- v. 85.- p. 662-632.

123. Rosenberg S.A., Lotze B., Yang J.C. et al. Prospective randomized trial of high dose of IL-2 alone and in conjugation with LAK for treatment of patients with advanced cancer/J. Natl. Cancer Inst. 1993.—v. 85.— P. 662-632.

124. S. Rueckert, I. Ruehl, S. Kahlert, G. Konecny, M. Untch. A monoclonal antibody as an effective therapeutic agent in breast cancer: Trastuzumab. Expert Opin. Biol. Ther. 2005 5 (6), 853-866.

125. Sato T. Locoregional immuno(bio)therapy for liver metastases. Semin Oncol*. 2002;29(2):160-7.

126. Savas B, Cole SP, Tsuruo T, Pross HF. P-glycoprotein-mediated' multidrug resistance and lymphokine-activated killer cell susceptibility in ovarian carcinoma. J Clin Immunol. 1996;16:348-357.

127. Savas B, Kerr PE, Ustun H, Cole SP, Pross HF. Lymphokine-activated killer cell susceptibility and multidrug resistance in small cell lung carcinoma. Anticancer Res. 1998;18:4355-4361.

128. Savas B, Arslan G, Gelen T, Karpuzoglu G, Ozkaynak C. Multidrug resistant malignant melanoma with intracranial metastasis responding to immunotherapy. Anticancer Res. 1999;19:4413^1420.

129. Savas Burhan, Pauline E Kerr, and Hugh F Pross Lymphokine-activated killer cell susceptibility and adhesion molecule expression of multidrug resistant breast carcinoma .Cancer Cell Int. 2006; 6: 24.

130. Scott P. Initiation cytokine for cell-mediated immunity. Science. 1993;260:496^197.

131. Schantz SP, Campbell BH, Guillamondegui OM: Pharyngeal carcinoma and natural killer cell activity. Am J Surg. 1986; 152: 467-474.

132. Schantz SP, Savage HE, Racz T, Taylor DL, Sacks PG. Natural killer cells and' metastases from pharyngeal carcinoma. Am J Surg. 1989; 158: 361-366.

133. Schantz SP and Ordonez NG. Quantitation of natural killer cell function and risk of metastatic poorly differentiated head and neck cancer. Nat Immun Cell Growth Regul. 1991; 10: 278-288.

134. Schiller J.H., Harrington D., Belani C.P. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. //N. Engl. J. Med. -2002.-vol.346.-p.92-98.

135. Schultze J, Nadler LM, Gribben JG. B7-mediated co stimulation and the immune response. Blood Rev. 1996; 10:111-27.

136. Schwarz RE, NL Vujanovic, and JC Hiserodt «Enhanced antimetastatic activity of lymphokine-activated killer cells purified and expanded by their adherence to plastic»Cancer research.-1989.-vol.49.-p. 1441-1446.

137. Seltzer V, Doyle A, Kadish AS. Natural cytotoxicity in malignant and premalignant cervical neoplasia and enhancement of cytotoxicity with interferon. Gynecol Oncol. 1983; 15: 340-349.

138. Semino C, Martini L, Queirolo P, Cangemi G, Costa R, Alloisio A, Ferlazzo G, Sertoli MR, Reali UM, Ratto GB, Melioli G. «Adoptive immunotherapy of advanced solid tumors: an eight year clinical experience.» Anticancer Res. 1999 Nov-Dec; 19(6C):5645-9.

139. Shah M.A., Schwartz G.K. Cell cycle-mediated drug resistance: an emerging concept.// Clin. Cancer Res.-2001 .-vol.7.-p.2168-2181.

140. Shankaran V, Ikeda H, Bruce AT, White JM, Swanson PE, Old LJ, et al. IF№ and lymphocytes prevent primary tumour development and shape tumour immunogenicity. Nature 2001; 410: 1107-1111.

141. Shiiba K., Suzuki R., Kawakami K. et al. Interleukin-2-activated killer cells: generation in collaboration with interferon and with supressor in cancer patients / Cancer Immunol. Immunother. 1986.— Vol. 21—P. 119-128.

142. Shiloni E, Eisenthal A, Sachs D, Rosenberg SA. Antibody-dependent cellular cytotoxicity mediated by murine lymphocytes activated in recombinant interleukin 2. J Immunol. 1987; 138(6): 1992-1998.

143. Shu S, Ghou T, Rosenberg SA. In vitro sensitization and expansion with viable tumor, cells and interleukin 2 in the generation of specific therapeutic effector cells. J Immunol. 1986; 136(10):3891-3898.

144. Shu SY, Chou T, Rosenberg SA. Generation from tumor-bearing mice of lymphocytes with in vivo therapeutic efficacy. J Immunol. 1987;139(l):295-304.

145. Sibbitt WLJr, Bankhurst AD, Jumonville AJ, Saiki J, Saiers JH, Doberneck RC. Defects in natural killer cell activity and interferon response in human lung carcinoma and malignant melanoma. Cancer Res. 1984; 44: 852-856.

146. Smith MR. Rituximab (monoclonal anti-CD20 antibody): mechanisms of action and resistance. Oncogene. 2003;22:7359-7368.

147. Smith MR. Rituximab (monoclonal anti-CD20 antibody): mechanisms of action and resistance. Oncogene. 2003;22:7359-7368.

148. Smyth MJ, Thia KY, Street SE, MacGregor D, Godfrey DI, Trapani JA. Perforin-mediated cytotoxicity is critical for surveillance of spontaneous lymphoma. J Exp Med. 2000; 192: 755-760.

149. Soda H., Koda K., Yasutomi J. et al Adoptive immunotherapy for advanced cancer patients using in vitro activated cytotoxic T lymphocytes.// J. Surg. Oncol. 1999. —- Vol. 72.— P. 211-217.

150. Song S.Y., Kim H.S. Srategy to improve DC -based immunotherapy against csncerYones Med. J.2004.- vol.45.-p.48-52.

151. Sorenson C.M., Eastman* A. Mechanismof cis-diamminedicioroplatinum(II)-indused cytotoxicity: role of G2 arrest and DNA double strand breaks.// Cancer Res.- 1988.-vol.48.-p.4484-4488.

152. Steven A. Rosenberg «Адоптивная иммунотерапия: клиническое применение». («Биологические методы лечения онкологических заболеваний» под редакцией Т.ДеВита, С.Хеллмана, С.Розенберга. М.: Медицина 2002).

153. Strand S, Galle PR. Immune evasion by tumours: involvement of the CD95 (APO-l/Fas) system and its clinical implications. Mol Med Today. 1998; 4:63-8.

154. Strayer DR, Carter WA, Mayberry SD, Pequignot E, Brodsky I. Low natural cytotoxicity of peripheral blood mononuclear cells in individuals with high familial incidences of cancer. Cancer Res. 1984; 44: 370-374.

155. Street SE, Cretney E, Smyth MJ. Perforin and interferon-7 activities independently control tumor initiation, growth, and metastasis. Blood. 2001; 97: 192-197.

156. Sullivan JL, Byron KS, Brewster FE, Purtilo DT. Deficient natural killer cell activity in X-linked lymphoproliferative syndrome. Science. 1980; 210: 543-545.

157. Sundstrom C, Nilsson K. Establishment and characterization of a human histiocytic lymphoma cell line (U937). Int J Cancer. 1976;17:565-577.

158. Takeda K, Smyth MJ, Cretney E, Hayakaw Y, Kayagaki N, Yagita H, et al. Critical role for tumor necrosis factor-related apoptosis-inducing ligand in immune surveillance against tumor development. J Exp Med. 2002; 195: 161-169.

159. Talmadge JE, Meyers KM, Prieur DJ, Starkey JR. Role of NK cells in tumour growth and metastasis in beige mice. Nature. 1980; 284: 622-624.

160. Tanaka K, Yoshioka T, Bieberich C, Jay C. Role of major histocompatibility complex class I antigens in tumor growth and metastasis. Annu Rev Immunol. 1988; 6:359-80.

161. Taniguchi T, Matsui H, Fujita T, Takaoka C, Kashima N, Yoshimoto R, Hamuro J. Structure and expression of a cloned cDNA for human interleukin-2. Nature. 1983;302(5906):305-310.

162. Tetu B, Brisson J. Prognostic sognoficance of Her-2neu oncoprotein expression in node-positive breast cancer: The influence of the pattern of immunostaining and adjuvant therapy. Cancer. 1994; 73: 2359-65.

163. Timonen T, Ortaldo JR, Herberman RB. Characteristics of human, large granular lymphocytes and relationship to natural killer and K cells. Jour Exp Med. 1981;153:569-582.

164. Thompson CB. Distinct roles for the costimulatory ligands B7-1 and B7-2 in T helper cell differentiation? Cell. 1995; 81:979-82.

165. Trinchieri G, Matsumoto-Kobayashi M, Clark SC, Seehra J, London L, Perussia B. Response of resting human peripheral blood natural killer cells to interleukin 2. TExp Med. 1984; 160: 1147-1169.

166. Trinchieri G. Interleukin-12:A proinflammatory cytokine with immunoregulatory functions that bridge innate resistance and antigen-specific adaptive immunity. Ann Rev Immunol. 1995;13:251-276.

167. Une Y, Kawata A, Uchino J. Adopted immunochemotherapy using IL-2 andsspleen LAK cell-randomized study. Nippon Geka Gakkai Zasshi 1991; 92: 13301333.

168. Vollenweider Iren, Moser René, Groscurth Peter. «Development of four donor-specific phenotypes in human long-term lymphokine-activated killer cell cultures." Cancer Immunology, Immunotherapy Issue: Volume 39, Number 5 Pages: 305 — 312.

169. Wang I, Fan P, Lu S Suppression of host Thl-type granulomatous inflammation by Taenia solium metacestodes is related to down-regulation of osteopontin gene expression International J.Parasitology. 2008.- vol. 38.- p. 239-248.

170. Yron I, Wood TA Jr, Spiess PJ, Rosenberg SA. In vitro growth of murine T cells. V. The isolation and growth of lymphoid cells infiltrating syngeneic solid tumors. J Immunol. 1980;125(l):238-245.

171. Zheng Y.J., Zhang J., Wang S.M., Zhang J.R. Morphological observation on NK/LAK cell-mediated lysis of human oral carcinoma JunYi Da Xue Xue Bao.-2004.-vol.-24.-p.392~396.

172. Zhonghua Zhong Liu Za Zhi. Some immune functions of patients with carcinoma. 1994 ;16(6):415-8.

173. Zhu L, chow LW, Loo WT et al. Her2neu expression predicts the response to antiaromatase neoadjuvant therapy in primary breast cancer: subgroup analysis from celecoxib antiaromatase neoadjuvant trial. Clin Cancer Res. 2004; 10 (14): 4639-4644.

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