Programming the anti-tumor immune response in vitro and its application to stop the growth of tumor cells and prolonging the lifespan of mice with carcinoma in vivo
Keywords:
macrophages; lymphocytes; carcinoma; reprogramming, immune response.
Abstract
Aim. To test a hypothesis that a combined pool of in vitro reprogrammed macrophages and lymphocytes will effectively limit growth of tumor cells in vitro, and injections of these cells into the body will considerably limit development of a tumor in vivo. Methods. Tumor growth was initiated in vitro by addition of Ehrlich carcinoma (EC) cells to the RPMI-1640 cell culture medium and in vivo by intraperitoneal injection of EC cells into mice. Results. M3-STAT3/6-SMAD3 macrophages in combination with antigen-reprogrammed lymphocytes exerted a pronounced antitumor effect both in vitro and in vivo, which was superior to the effect of cisplatin. Conclusion. M3 macrophages in combination with in vitro antigen-reprogrammed lymphocytes significantly inhibited the tumor growth in vivo. This fact justifies development of a clinical version of the tumor growth restricting biotechnology using pre-programming of the antitumor immune response in vitro.
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References
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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.
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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.
11. Sharma M. Chemokines and their receptors: orchestrating a fine balance between health and disease. Critical Reviews in Biotechnology. 2009; 30(1): 1-22.
12. Dunn G.P., Old L.J., Schreiber R.D. The immunobiology of cancer immunosurveillance and immunoediting. Immunity. 2004; 21(2): 137-48.
13. Khong H.T., Restifo N.P. Natural selection of tumor variants in the generation of «tumor escape» phenotypes. Nature Immunology. 2002; 3(11): 999-1005.
14. Zou W. Regulatory T cells, tumor immunity and immunotherapy. Nature Reviews Immunology. 2006; 6(4): 295-307.
15. Stout R.D., Watkins S.K., Suttles J. Functional plasticity of macrophages: in situ reprogramming of tumor-associated macrophages. Journal of Leukocyte Biology. 2009; 86(5): 1105-9.
16. Malyshev I., Malyshev Yu. Current concept and update of the macrophage plasticity concept: intracellular mechanisms of reprogramming and M3 macrophage «switch» phenotype. BioMed Research International. 2015; 2015: 341308.
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.
23. Becker G., Galandi D., Blum H.E. Malignant ascites: systematic review and guideline for treatment. European Journal of Cancer. 2006; 42(5): 589-97.
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.
28. Zhang X., Goncalves R., Mosser D.M. The Isolation and Characterization of Murine Macrophages. Current Protocols in Immunology. 2008; Chapter 14: Unit 14.1.
29. Martinez F.O., Sica A., Mantovani A., Locati M. Macrophage activation and polarization. Frontiers in Bioscience. 2008; 1(13): 453-61.
30. Briard J.G., Poisson J.S., Turner T.R., Capicciotti C.J., Acker J.P., Ben R.N. Small molecule ice recrystallization inhibitors mitigate red blood cell lysis during freezing, transient warming and thawing. Scientific reports. 2016; 6: 23619.
31. Goldberg S. Mechanical/physical methods of cell disruption and tissue homogenization. Methods in molecular biology (Clifton, N.J.). 2008; 424: 3-22.
32. Lejtenyi D., Osmond D.G., Miller S.C. Natural killer cells and B lymphocytes in L-selectin and Mac-1/LFA-1 knockout mice: marker-dependent, but not cell lineage-dependent changes in the spleen and bone marrow. Immunobiology. 2003; 207(2): 129-35.
33. Roco A., Cayun J., Contreras S., Stojanova J., Quiсones L. Can pharmacogenetics explain efficacy and safety of cisplatin pharmacotherapy? Frontiers in Genetics. 2014; 5: 391.
34. Chen T.C., Cho H.Y., Wang W., Wetzel S.J., Singh A., Nguyen J. et al. Chemotherapeutic effect of a novel temozolomide analog on nasopharyngeal carcinoma in vitro and in vivo. Journal of Biomedical Science. 2015; 22(1): 71.
35. Noёl W., Raes G., Hassanzadeh Ghassabeh G., De Baetselier P., Beschin A. Alternatively activated macrophages during parasite infections. Trends in Parasitology. 2004; 20(3): 126-33.
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37. Satoh T., Saika T., Ebara S., Kusaka N., Timme T.L., Yang G. et al. Macrophages transduced with an adenoviral vector expressing IL-12 suppress tumor growth and metastasis in a preclinical metastatic prostate cancer model. Cancer Research. 2003; 63(22): 7853-60.
38. Baay M., Brouwer A., Pauwels P., Peeters M. and Lardon F. Tumor cells and tumor-associated macrophages: secreted proteins as potential targets for therapy. Clinical and Developmental Immunology. 2011; 2011: 565187.
39. Aharinejad S., Abraham D., Paulus P., Abri H., Hofmann M., Grossschmidt K. Colony-stimulating factor-1 antisense treatment suppresses growth of human tumor xenografts in mice. Cancer Research. 2002; 62(18): 5317-24.
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.
Published
2017-12-18
How to Cite
Kalish S. V., Lyamina S. V., Raetskaya A. A., Budanova O. P., Malyshev I. Y. Programming the anti-tumor immune response in vitro and its application to stop the growth of tumor cells and prolonging the lifespan of mice with carcinoma in vivo // Patologicheskaya Fiziologiya i Eksperimental’naya Terapiya (Pathological physiology and experimental therapy). 2017. VOL. 61. № 4. PP. 67–73.
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Section
Original research
