Программирование противоопухолевого иммунного ответа in vitro и его использование для остановки пролиферации опухолевых клеток и увеличения продолжительности жизни мышей с карциномой in vivo
Ключевые слова:
макрофаги, лимфоциты, карцинома, репрограммирование, иммуный ответ.
Аннотация
Цель — представить доказательства правомерности гипотезы, что комбинированный пул репрограммированных in vitro макрофагов и лимфоцитов будет эффективно ограничивать пролиферацию опухолевых клеток in vitro, а при введении в организм будет существенно ограничивать развитие опухоли in vivo. Методика. Размножение опухолевых клеток инициировали in vitro путем добавления клеток карциномы Эрлиха (КЭ) в среду культивирования RPMI-1640. Развитие асцитной опухоли in vivo воспроизводили путем внутрибрюшной инъекции клеток КЭ мышам. Результаты. Установлено, что M3-STAT3/6-SMAD3 макрофаги вместе с антиген-репрограммированными лимфоцитами оказывают выраженный противоопухолевый эффект и in vitro, и in vivo, который был существеннее противоопухолевого эффекта цисплатина. Заключение. Факты, свидетельствующие, что М3 макрофаги в сочетании с in vitro антиген-репрограммированными лимфоцитами значительно подавляют рост опухоли in vivo, делают перспективным разработку клинической версии биотехнологии ограничения роста опухоли путем предварительного программирования противоопухолевого иммунного ответа «в пробирке».
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Литература
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2. Sica A., Schioppa T., Mantovani A., Allavena P. Tumor-associated macrophages are a distinct M2 polarized population promoting tumor progression: potential targets of anti-cancer therapy. European Journal of Cancer. 2006; 42(6): 717-27.
3. Mills C.D., Thomas A.C., Lenz L.L., Munder M. Macrophage: SHIP of Immunity. Frontiers in Immunology. 2014; 5: 620.
4. Mills C.D., Kincaid K., Alt J.M., Heilman M.J., Hill A.M. M-1/M-2 macrophages and the Th1/Th2 paradigm. The Journal of Immunology. 2000; 164(12): 6166-73.
5. Rey-Giraud F., Hafner M., Ries C.H. In vitro generation of monocyte-derived macrophages under serum-free conditions improves their tumor promoting functions. PLoS One. 2012; 7(8): e42656.
6. Gordon S., Taylor P.R. Monocyte and macrophage heterogeneity. Nature Reviews Immunology. 2000; 5: 953-964.
7. Mantovani A., Sozzani S., Locati M., Allavena P., Sica A. Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends in Immunology. 2002; 23(11): 549-55.
8. Zeini M., Travеs P.G., Lоpez-Fontal R., Pantoja C., Matheu A., Serrano M. et al. Specific contribution of p19 (ARF) to nitric oxide-dependent apoptosis. The Journal of Immunology. 2006; 177(5): 3327-36.
9. Tsung K., Dolan J.P., Tsung Y.L., Norton J.A. Macrophages as effector cells in interleukin 12-induced T cell-dependent tumor rejection. Cancer Research. 2002; 62(17): 5069-75.
10. Ibe S., Qin Z., Schuler T., Preiss S., Blankenstein T. Tumor rejection by disturbing tumor stroma cell interactions. The Journal of Experimental Medicine. 2001; 194(11): 1549-1559.
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17. Gabrilovich D. Mechanisms and functional significance of tumor-induced dendritic-cell defects. Nature Reviews Immunology. 2004; 4 (12): 941-52.
18. Kono Y., Kawakami S., Higuchi Y., Maruyama K., Yamashita F., Hashida M. Antitumor effect of nuclear factor-kB decoy transfer by mannose-modified bubble lipoplex into macrophages in mouse malignant ascites. Cancer Science. 2014; 105(8): 1049-55.
19. Kalish S.V., Lyamina S.V., Usanova E.A., Manukhina E.B., Larionov N.P., Malyshev I.Yu. Macrophages reprogrammed in vitro towards the M1 phenotype and activated with LPS extend lifespan of mice with ehrlich ascites carcinoma. Medical Science Monitor Basic Research. 2015; 21: 226-34.
20. Kalish S., Lyamina S., Manukhina E., Malyshev Y., Raetskaya A., Malyshev I. M3 Macrophages Stop Division of Tumor Cells In Vitro and Extend Survival of Mice with Ehrlich Ascites Carcinoma. Medical science monitor basic research. 2017; 23: 8-19.
21. Gabrilovich D. Mechanisms and functional significance of tumour-induced dendritic-cell defects. Nature reviews. Immunology. 2004; 4(12): 941-52.
22. Cavazzoni E., Bugiantella W., Graziosi L., Franceschini M.S., Donini A. Malignant ascites: pathophysiology and treatment. International Journal of Clinical Oncology. 2013; 18(1): 1-9.
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24. Ahmed N., Stenvers K.L. Getting to know ovarian cancer ascites: opportunities for targeted therapy-based translational research. Frontiers in Oncology. 2013; 3: 256.
25. Saif M.W., Siddiqui I.A., Sohail M.A. Management of ascites due to gastrointestinal malignancy. Annals of Saudi Medicine. 2009; 29(5): 369-77.
26. Kono Y., Kawakami S., Higuchi Y., Maruyama K., Yamashita F., Hashida M. Antitumor effect of nuclear factor-kB decoy transfer by mannose-modified bubble lipoplex into macrophages in mouse malignant ascites. Cancer Science. 2014; 105(8): 1049-55.
27. Ray T., Chakrabarti M.K., Pal A. Hemagglutinin protease secreted by V. cholerae induced apoptosis in breast cancer cells by ROS mediated intrinsic pathway and regresses tumor growth in mice model. Apoptosis. 2016; 21(2): 143-54.
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29. Martinez F.O., Sica A., Mantovani A., Locati M. Macrophage activation and polarization. Frontiers in Bioscience. 2008; 1(13): 453-61.
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31. Goldberg S. Mechanical/physical methods of cell disruption and tissue homogenization. Methods in molecular biology (Clifton, N.J.). 2008; 424: 3-22.
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36. Peng J., Tsang J.Y., Li D., Niu N., Ho D.H., Lau K.F. et al. Inhibition of TGF-b signaling in combination with TLR7 ligation re-programs a tumoricidal phenotype in tumor-associated macrophages. Cancer Letters. 2013; 331(2): 239-49.
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40. Malyshev I.Yu. Phenomena and signaling mechanisms reprogramming of macrophages. Patologicheskaya fiziologiya i eksperimental’naya terapiya. 2015; 59(2): 99-111. (in Russian)
41. Lee P.P., Yee C., Savage P.A., Fong L., Brockstedt D., Weber J.S., Johnson D., Swetter S., Thompson J., Greenberg P.D., Roederer M., Davis M.M. Characterization of circulating T cells specific for tumor-associated antigens in melanoma patients. Nature medicine. 1999; 5(6): 677-85.
Опубликован
2017-12-18
Как цитировать
Калиш С. В., Лямина С. В., Раецкая А. А., Буданова О. П., Малышев И. Ю. Программирование противоопухолевого иммунного ответа in vitro и его использование для остановки пролиферации опухолевых клеток и увеличения продолжительности жизни мышей с карциномой in vivo // Патологическая физиология и экспериментальная терапия. 2017. Т. 61. № 4. С. 67–73.
Выпуск
Раздел
Оригинальные исследования
