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New capabilities of regulation of antitumor immune response

https://doi.org/10.18027/2224-5057-2015-1-24-30

Abstract

The tumor has different mechanisms capable of destroying the immunological protection. Population of regulatory cells, along with other factors provide “escape” of the tumor from immune surveillance. In our laboratory, we studied the features of quantitative changes of some subpopulations of peripheral blood lymphocytes in primary operable breast cancer (BC) and melanoma at different stages of tumor growth and in the process of tumor therapy. In 94.5% of patients with breast cancer were found to increase compared to the control amount of NKT-cells with the phenotype CD45+CD3+ CD16+CD56+, 78% increase in number of CD8+CD28– T-cells, and 20.5% increase in the number of patients Regulatory CD4+CD25+FOXP3+ T cells. Was found to depend on changes in the number of these cells from the stage of the disease. Patients with stage I and II disease there was a statistically significant increase in the percentage of CD8+CD28– T–cells and CD45+CD3+ CD16+CD56+ NKT-cells compared to the donor. At the same time in patients with stage III the number of cells of both populations declined and did not differ from the norm. Such dynamics of quantitative changes were typical for the main populations of effector cells antitumor immunity. In the evaluation of patients with disseminated melanoma was found that no increase in the number of cytotoxic CD45+CD8+CD11b+ T cells in the treatment dendritic cell vaccine (DCV) appears to be an indication to stop vaccine therapy, initially increased amount of CD3+CD8+CD16+. NKT-cells may serve as grounds for refusal of DCV. A brief description of the major co-receptor inhibitor of T-cells, and monoclonal antibodies that block the inhibitory molecule on immune and tumor cells in order to increase the efficiency of anti-tumor immune response. Encouraging clinical results have been obtained by using anti-CTLA-4 (ipilimumab), and anti-PD-1 (nivolumab) monoclonal antibodies.

About the Authors

Z. G. Kadagidze
НИИ клинической онкологии ФГБУ «РОНЦ им. Н. Н. Блохина»
Russian Federation


A. I. Chertkova
НИИ клинической онкологии ФГБУ «РОНЦ им. Н. Н. Блохина»
Russian Federation


T. N. Zabotina
НИИ клинической онкологии ФГБУ «РОНЦ им. Н. Н. Блохина»
Russian Federation


O. V. Korotkova
НИИ клинической онкологии ФГБУ «РОНЦ им. Н. Н. Блохина»
Russian Federation


E. G. Slavina
НИИ клинической онкологии ФГБУ «РОНЦ им. Н. Н. Блохина»
Russian Federation


A. A. Borunova
НИИ клинической онкологии ФГБУ «РОНЦ им. Н. Н. Блохина»
Russian Federation


References

1. Kadagidze Z.G., Chertkova A.I., Slavina E.G. NKT-cells and antitumor immunity. RBZh. 2011. vol.11, no.3, p.9–15.

2. Kadagidze Z.G., Chertkova A.I., Slavina E.G. Regulatory T-cells and its role in antitumor immune response. Voprosy Onkologii [Questions in Oncology]. 2009. vol.55, p.269–277.

3. Berzofsky J. A., Terabe M. NKT cells in tumor immunity: opposing subsets define a new immunoregulatory axis. // J. Immunol.— 2008.— Vol. 180.— P. 3627–3635.

4. Berzofsky J. A., Terabe M. The contrasting roles of NKT cells in tumor immunity // Curr. Mol. Med.— 2009.— Vol. 9.— P. 667–672.

5. Bulliard Y., Jolicoeur R,. Windman M. et al. Activating Fc receptors contribute to the antitumor activities of immunoregulatory receptor-targeting antibodies // J. Exp. Med.— 2013.— Vol.210.— P.1685–1693.

6. deLeeuw R.J., Kost S.E, Kakal J. A. et al. The prognostic value of FoxP3+ tumor-infiltrating lymphocytes in cancer: a critical review of the literature. // Clin. Cancer Res.— 2012.— Vol. 18.— P. 3022–3029.

7. Dieu-Nosjean M–C., Antoine M., Danel C. Et al. Long-term survival for patients with non–small-cell lung cancer with intratumoral lymphoid structures // J. Clin. Oncol.— 2008.— Vol. 26.— P. 4410–4417. 4410–4417.

8. Eiro’N., Pidal I., Fernandez-Garcia B. et al. Impact of CD68/ (CD3+CD20) ratio at the invasive front of primary tumors on distant metastasis development in breast cancer // PLOS one.— 2012.— Vol.7.— Issue 12 — P. e52796. pone 0052796.

9. Facciabene A., Motz G. T., Coukos G. T-regulatory cells: key players in tumor immune escape and angiogenesis // Cancer Res.— 2012 Vol.— 72.— P. 2162–2171.

10. Filaci G., Fenoglio D., Fravega M. CD8+CD28- T regulatory lymphocytes inhibiting T cell proliferative and cytotoxic functions infiltrate human cancers // J. Immunol.— 2007.— Vol. 179.— P. 4323–4334.

11. Filaci G., Rizzi M., Setti M. et al. Non-antigen-specific CD8+ T suppressor

12. lymphocytes in diseases characterized by chronic immune responses and inflammation // Ann. NY Acad. Sci.— 2005.— Vol. 1050. P. 115–123.

13. Finn O. J. Immuno-oncology: understanding the function and dysfunction of the immune system in cancer // Ann Oncol.— 2012.— Suppl. 8viii 6–9.

14. Hald S. M., Bremnes R. M., Al-Shibli K. et al. CD4/ CD8 co-expression shows independent prognostic impact in resected non-small cell lung cancer patients treated with adjuvant radiotherapy // Lung Cancer.— 2013.— Vol. 80.— P. 209–215. 209–215.

15. Hino R, Kabashima K,, Kato Y. et al. Tumor cell expression of programmed cell death-1 ligand 1 is a prognostic factor for malignant melanoma // Cancer.— 2010.— Vol. 116 — P. 1757–1766.

16. Hodi F.S., Butler M., Oble D.A. et al. Immunologic and clinical effects of antibody blockade of cytotoxic T lymphocyte-associated antigen 4 in previously vaccinated cancer patients // Proc. Natl. Acad. Sci. U S A.— 2008.— Vol.105.— P.3005–3010.

17. Hodi F. S., O’Day S.J., McDermott D.F. et al. Improved survival with ipilimumab in patients with metastatic melanoma // N. Engl. J. Med.— 2010.— Vol. 363 — P.711–723.

18. Izhak L., Ambrosino E., Kato S. et al. Delicate balance among three types of T cells in concurrent regulation of tumor immunity // Cancer Res.— 2013.— Vol. 73. P. 1514–1523.

19. Karag z B., Bilgi O., G m s M. et al.CD8+CD28– cells and CD4+CD25+ regulatory T cells in the peripheral blood of advanced stage lung cancer patients // Med. Oncol.— 2010.— Vol. 27.— P. 29–33.

20. Keir M. E., Butte M. J., Freeman G. J., Sharpe A. H. PD-1 and its ligands in tolerance and immunity // Annu. Rev. Immunol.— 2008.— Vol. 26.— P.677–704.

21. Kim P. S., Ahmed R. Features of responding T cells in cancer and chronic infection // Curr. Opin. Immunol.— 2010.— Vol. 22 — P. 223–230.

22. Kyi C., Postow M. A. Checkpoint blocking antibodies in cancer immunotherapy // FEBS Lett.— 2014.— Vol. 588.— P. 368–376.

23. Li S-Y., Liu Y. Immunotherapy of melanoma with the immune costimulatory monoclonal antibodies targeting CD137 // Clinical Pharmacol: Adv. Appl.— 2013.— Vol.5 (Suppl 1) — P. 47–53.

24. Liakou C. I., Kamat A., Tang D. N. CTLA-4 blockade increases IFNgamma-producing CD4+ICOShi cells to shift the ratio of effector to regulatory T cells in cancer patients // Proc. Natl. Acad. Sci.U S A.— 2008.— Vol.105.— P.14987–14992.

25. Lippitz B. E. Cytokine patterns in patients with cancer: a systematic review // Lancet Oncol.— 2013.— Vol.14.— P. e218-e228.

26. Meloni F., Morosini M., Solari N. et al. Foxp3 expressing CD4+CD25+ and CD8+CD28– T regulatory cells in the peripheral blood of patients with lung cancer and pleural mesothelioma // Hum Immunol.— 2006.— Vol. 67.— P. 1–12.

27. Monu N. R., Frey A. B. Myeloid-derived suppressor cells and anti-tumor T cells: a complex relationship // Immunol. Invest.— 2012.— Vol. 41.— P. 595–613.

28. Najafian N., Chitnis T., Salama A.D, et al. Regulatory functions of CD8+CD28- T cells in an autoimmune disease model // J Clin Invest.— 2003.— Vol. 112.— P.1037–1048.

29. Postow M. A., Harding J., Wolchok J. D. Targeting immune checkpoints: releasing the restraints on anti-tumor immunity for patients with melanoma // Cancer J.— 2012.— Vol. 18 — P. 153–159.

30. Quezada S. A., Peggs K. S., Curran M. A., Allison J. P. CTLA4 blockade and GM–CSF combination immunotherapy alters the intratumor balance of effector and regulatory T cells // J. Clin. Invest.— 2006.— Vol.116.— P.1935–1945.

31. Senovilla L., Vacchelli E., Galon J. et al. Prognostic and predictive value of the immune infiltrate in cancer // OncoImmunol.— 2012.— Vol. 1 — P.1323–1343.

32. Simpson T. R., Li F., Montalvo-Ortiz W. et al. Fc-dependent depletion of tumor-infiltrating regulatory T cells co-defines the efficacy of anti-CTLA-4 therapy against melanoma // J. Exp. Med.— 2013.— Vol. 210.— P. 1695–1710.

33. Subleski J. J., Jiang Q., Weiss J. M., Wiltrout R. H. The split personality of NKT cells in malignancy, autoimmune and allergic disorders // Immunotherapy.— 2011.— Vol. 10.— P. 1167–1184.

34. Tarhini A. A., Edington H., Butterfield L. H. et al. Immune monitoring of the circulation and the tumor microenvironment in patients with regionally advanced melanoma receiving neoadjuvant ipilimumab // PLoS One.— 2014.— Vol. 9.— P. e87705.

35. Urbaniak-Kujda D., Kapelko-S owik K., Wo owiec D. et al. Increased percentage of CD8+CD28- suppressor lymphocytes in peripheral blood and skin infiltrates correlates with advanced disease in patients with cutaneous T-cell lymphomas // Postepy Hig Med Dosw.— 2009.— Vol. 63.— P. 355–359.

36. Vigan S., Perreau M., Pantaleo G., Harari A. Positive and negative regulation of cellular immune responses in physiologic conditions and diseases // Clin. Dev. Immunol.— 2012.— Vol. 2012–485781.

37. Vonderheide R. H., Flaherty K. T., Khalil M. et al. Clinical activity and immune modulation in cancer patients treated with CP-870,893, a novel CD40 agonist monoclonal antibody // J Clin Oncol.— 2007.— Vol. 25 — P. 876–883.

38. Voron T., Marcheteau E., Pernot S.et al. Control of the immune response by pro-angiogenic factors // Front. Oncol.— 2014.— Vol. 4 — Article.70.

39. Wang S., Chen L. T lymphocyte co-signaling pathways of the B7-CD28 family // Cell Mol. Immunol.— 2004.— Vol. N 1.— P. 37–42.

40. Watanabe N., Nakajima H. Coinhibitory molecules in autoimmune diseases. Clin. Dev. Immunol.— 2012.— Vol. 2012–269756.

41. Weinberg A. D., Morris N.P., Kovacsovics-Bankowski M. et al. Science gone translational: the OX40 agonist story// Immunol Rev.— 2011.— Vol. 244 — P. 218–231.

42. West E. E., Jin H-T., Rasheed A-U. PD-L1 blockade synergizes with IL-2 therapy in reinvigorating exhausted T cells // J. Clin. Invest.— 2013.— Vol. 123 — P. 2604–2615.

43. Wherry E. J., Ha S. J., Kaech S. M. Molecular signature of CD8+ T cell exhaustion during chronic viral infection // Immunity.— 2007.— Vol. 27 — P. 670–684.

44. Whiteside T. L. What are regulatory T cells (Treg) regulating in cancer and why? // Semin. Cancer Biol.— 2012.— Vol. 22.— P. 327–334.

45. Wolchok J. D., Kluger H., Callahan M. K. et al. Nivolumab plus ipilimumab in advanced melanoma // N. Engl. J. Med.— 2013.— Vol.369.— P.122–133


Review

For citations:


Kadagidze Z.G., Chertkova A.I., Zabotina T.N., Korotkova O.V., Slavina E.G., Borunova A.A. New capabilities of regulation of antitumor immune response. Malignant tumours. 2015;(1):26-34. (In Russ.) https://doi.org/10.18027/2224-5057-2015-1-24-30

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ISSN 2224-5057 (Print)
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