Features of effector lymphocyte subsets in patients with uveal melanoma in recurrent and chronic herpesvirus infection

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Abstract

The aim of the study is to conduct a comparative analysis of percentages for peripheral blood effector lymphocyte subsets in patients with uveal melanoma manifested by recurrent and chronic herpesvirus infection. There were 141 subjects enrolled: 70 patients with uveal melanoma, 38 patients with corneal ulcers and involvement of the uveal tract as well as 33 healthy donors. Immunophenotyping was performed by using laser flow cytometry with panel of monoclonal antibodies to differentiate lymphocyte subpopulations. IgM and IgG antibodies to herpesvirus infections were determined by using enzyme-linked immunosorbent assay on an automatic ELISA analyzer Lazurit (USA) with diagnostic kits of CJSC “Vector-Best” (Koltsovo). The data obtained showed that the absolute number of blood lymphocytes (CD45+) in patients with uveal melanoma did not differ from those in healthy donors. In contrast, patients with corneal ulcers and involvement of the uveal tract had this parameter increased. A decreased relative and absolute count of T cells (CD3+) in uveal melanoma, but increased absolute CD3+ number in inflammation was observed. No difference in relative and absolute content of the CD3+CD4+ helper/inducer subpopulation in patients with recurrent herpesvirus infections was found. Corneal ulcers in cancer patients revealed significantly increased absolute level of CD3+CD4+ helpers/inductor cells. Chronic herpesvirus infection in uveal melanoma patients showed increased relative and absolute number of cytotoxic T lymphocytes (CD3+CD8+). Recurrent herpesvirus infection was featured with decreased relative number of T lymphocytes (CD3+CD8+), upon inflammation, there was noted increased absolute and decreased relative number compared with healthy subjects. Double positive T cells increased in tumor and inflammation. B lymphocytes (CD19+) increased in melanoma and inflammation. The relative number of blood natural killer cells (CD16+CD56+) in uveal melanoma increased upon recurrent infection. Inflammation was coupled to decreased relative level of natural killer cells (CD16+CD56+). Melanoma showed no changes in CD4+/ CD8+ ratio; upon inflammation, its increase was noted in acute and chronic herpesvirus infections (p < 0.05). The suppression of the immune system in uveal melanoma, restricting antiviral defense, was revealed. The data obtained seem to be important for development of personalized approaches to prognosis and treatment of patients with uveal melanoma.

About the authors

N. V. Balatskaya

Moscow Helmholtz Research Сentre of Eye Diseases

Email: myakoshina@mail.ru

PhD (Biology), Leading Researcher, Department of Immunology and Virology, Head of the Department of Immunology and Virology, Moscow Helmholtz Research Сentre of Eye Diseases.

105062, Moscow, Sadovaya-Chernogryazskaya str., 14/19.

Russian Federation

S. V. Saakyan

Moscow Helmholtz Research Сentre of Eye Diseases

Email: myakoshina@mail.ru

PhD, MD (Medicine), Professor, Head of the Department of Ophthalmooncology and Radiology, Moscow Helmholtz Research Centre of Eye Diseases.

105062, Moscow, Sadovaya-Chernogryazskaya str., 14/19.

Russian Federation

E. B. Myakoshina

Moscow Helmholtz Research Сentre of Eye Diseases

Author for correspondence.
Email: myakoshina@mail.ru
ORCID iD: 0000-0002-2087-7155

Elena B. Myakoshina - PhD (Medicine), Senior Researcher, Department of Ophthalmology and Radiology, Moscow Helmholtz Research Centre of Eye Diseases.

105062, Moscow, Sadovaya-Chernogryazskaya str., 14/19.

Phone: +7 916 196-90-30

Russian Federation

I. G. Kulikova

Moscow Helmholtz Research Сentre of Eye Diseases

Email: myakoshina@mail.ru

Senior Researcher, Department of Immunology and Virology, Moscow Helmholtz Research Centre of Eye Diseases.

105062, Moscow, Sadovaya-Chernogryazskaya str., 14/19.

Russian Federation

G. I. Krichevskaya

Moscow Helmholtz Research Сentre of Eye Diseases

Email: myakoshina@mail.ru

PhD (Medicine), Leading Researcher, Department of Immunology and Virology.

105062, Moscow, Sadovaya-Chernogryazskaya str., 14/19.

Russian Federation

References

  1. Абакушина Е.В., Кузьмина Е.Г., Коваленко Е.И. Основные свойства и функции NK-клеток человека // Иммунология. 2012. Т. 33, № 4. С. 220–224.
  2. Бровкина А.Ф., Панова И.Е., Саакян С.В. Офтальмоонкология: новое за последние два десятилетия // Вестник офтальмологии. 2014. Т. 130, № 6. С. 13–19.
  3. Воробьев А.А., Быковская С.Н., Пашков Е.П., Быков А.С. Роль клеток-регуляторов CD4+CD25+ в развитии хронических инфекционных заболеваний // Вестник РАМН. 2006. № 9–10. С. 24–29.
  4. Железникова Г.Ф. Регуляторные Т-лимфоциты в иммунном ответе на инфекцию // Журнал инфектологии. 2011. Т. 3, № 1. C. 6–13. doi: 10.22625/2072-6732-2011-3-1-6-13
  5. Кадагидзе З.Г., Черткова А.И., Заботина Т.Н., Короткова О.В., Славина Е.Г., Борунова А.А. Новые возможности регуляции противоопухолевого иммунного ответа // Злокачественные опухоли. 2015. Т. 1. С. 24–30. doi: 10.18027/2224-5057-2015-1-24-30
  6. Кричевская Г.И., Слепова О.С., Саакян С.В., Мякошина Е.Б. Влияние герпесвирусных инфекций на уровень сывороточного интерферона-альфа и интерферона-гамма у пациентов с начальной меланомой хориоидеи // Российский офтальмологический журнал. 2014. Т. 7, № 2. С. 28–32. doi: 10.18008/1816-5095-2019-1S-40-44
  7. Кричевская Г.И., Слепова О.С., Саакян С.В., Мякошина Е.Б., Андреева Т.А., Андрюшин А.Е., Хорошилова И.П., Захарова Г.П., Майбогин А.М., Трухина А.В. К вопросу о роли вирусов герпеса человека в патогенезе опухолей орбиты и глаза: детекция вирусной ДНК в биоптатах опухолей. Рoссийский офтальмологический журнал // 2016. Т. 2. С. 42–47. doi: 10.21516/2072-0076-2016-9-2-42-46
  8. Нероев В.В., Катаргина Л.А., Ковалева Л.А., Кричевская Г.И., Балацкая Н.В. Клинические аспекты бактериальной язвы роговицы затяжного течения, роль вирусов герпеса в ее патогенезе, тактика лечения // Офтальмология. 2019. Т. 16 (1S). С. 40–44. doi: 10.18008/1816-5095-2019-1S-40-44
  9. Патент № 2147373 Российская Федерация, МПК G01N33/53 (1998.06). Способ выявления скрытого метастазирования при увеальной меланоме: № 98111889/14; заявлено 19.06.1998: опубликовано 10.04.2000 / Лихванцева В.Г., Бровкина А.Ф., Гусев Г.А., Юровская Н.Н. Патентообладатель: Московский НИИ глазных болезней имени Гельмгольца. 9 с.
  10. Саакян С.В., Амирян А.Г., Цыганков А.Ю., Склярова Н.В., Залетаев Д.В. Клинические, патоморфологические и молекулярно-генетические особенности увеальной меланомы с высоким риском метастазирования // Российский офтальмологический журнал. 2015. Т. 8, № 2. С. 47–52.
  11. Саакян С.В., Мякошина Е.Б., Кричевская Г.И., Слепова О.С., Пантелеева О.Г., Андрюшин А.С., Хорошилова-Маслова И.П., Захарова Г.П. Обследование больных увеальной меланомой на наличие герпесвирусных инфекция // Вопросы вирусологии. 2016. Т. 61, № 6. С. 284–287. doi: 10.18821/0507-4088-2016-61-6-284-287
  12. Сорокина М.Н., Скрипченко Н.В. Вирусные энцефалиты и менингиты у детей. М.: Медицина, 2004. 416 с.
  13. Bronkhorst I.H.G., Vu T.H.K., Jordanova E.S., Luyten G.P.M., van der Burg S.H., Jager M.J. Different subsets of tumor-infiltrating lymphocytes correlate with macrophage influx and monosomy 3 in uveal melanoma. Invest. Ophthalmol. Vis. Sci., 2012, vol. 53, pp. 5370–5378. doi: 10.1167/iovs.11-9280
  14. Carvajal R.D., Schwartz G.K., Tezel T.H., Marr B., Francis J.H., Nathan P.D. Metastatic disease from uveal melanoma: treatment options and future prospects. Br. J. Ophthalmol., 2017, vol. 101, pp. 38–44. doi: 10.1136/bjophthalmol-2016-309034
  15. Collaborative Ocular Melanoma Study Group. Histopathologic characteristics of uveal melanomas in eyes enucleated from the Collaborative Ocular Melanoma Study. Am. J. Ophthalmol, 1998, vol. 125, pp. 745–766. doi: 10.1016/S0002-9394(98)00040-3
  16. Desfrancois J., Moreau-Aubry A., Vignard V., Godet Y., Khammari A., Dréno B., Jotereau F., Gervois N. Double positive CD4CD8 alpha beta T cells: a new tumor-reactive population in human melanomas. PLoS, 2010, vol. 5: e8437. doi: 10.1371/journal.pone.0008437
  17. Houghton A.N., Gold J.S., Blachere N.E. Immunity against cancer: lessons learned from melanoma. Curr. Opin. Immunol., 2001, vol. 13, pp. 134–140. doi: 10.1016/s0952-7915(00)00195-3
  18. Kawamura K., Kadowaki N., Kitawaki T., Uchiyama T. Virus-stimulated plasmacytoid dendritic cells induce CD4+ cytotoxic regulatory T cells. Blood, 2006, vol. 107, no. 3, pp. 1031–1038. doi: 10.1182/blood-2005-04-1737
  19. Lambert S.R., Char D.H., Howes E.J., Crawford J.B., Wells J. Spontaneous regression of a choroidal melanoma. Arch. Ophthalmol., 1986, vol. 104, pp. 732–734. doi: 10.1038/sj.eye.6702071
  20. Li L., Wu C. CD4+CD25+ Treg cells inhibit human memory γδT cells to produce IFN-γ in response to Mycobacterium tuberculosis antigen ESAT-6. Blood, 2008, vol. 111, no. 12, pp. 5629–5636. doi: 10.1182/blood-2008-02-139899
  21. Mantovani A. Tumor-associated macrophages in neoplastic progression: a paradigm for the in vivo function of chemokines. Lab. Invest., 1994, vol. 71, pp. 5–16.
  22. Mantovani A., Romero P., Palucka A.K., Marincola F.M. Tumour immunity: effector response to tumour and role of the microenvironment. Lancet, 2008, vol. 371, no. 9614, pp. 771–783. doi: 10.1016/S0140-6736(08)60241-X
  23. Moore P.S., Chang Y. Why do viruses cause cancer? Highlights of the first century of human tumour virology. Nat. Rev. Cancer, 2010, vol. 10, no. 12, pp. 878–889. doi: 10.1038/nrc2961
  24. Niederkorn J.Y. Immune escape mechanisms of intraocular tumors. Prog. Retin. Eye Res., 2009, vol. 28, pp. 329–347. doi: 10.1016/j.preteyeres.2009.06.002
  25. Oliva M., Rullan A.J., Piulats J.M. Uveal melanoma as a target for immune-therapy. Ann. Transl. Med., 2016, vol. 4, no. 9: 172. doi: 10.21037/atm.2016.05.04
  26. Priluck I.A., Robertson D.H., Pritchard P.J., Ilstrup D.M. Immune responsivness in patients with choroidal malignant melanoma. Am. S. Ophthalmol., 1979, vol. 87, pp. 215–220. doi: 10.1016/0002-9394(79)90146-6
  27. Tobal K., Deuble K., McCartney A., Lightman S. Characterization of cellular infiltration in choroidal melanoma. Melanoma Res., 1993, vol. 3, pp. 63–65.
  28. Wisnoski N., Chung C.-S., Chen Y., Huang X., Ayala A. The contribution of CD4+CD25+ T-regulatory cells to immune suppression in sepsis. Shock, 2007, vol. 27, no. 3, pp. 251–257. doi: 10.1097/01.shk.0000239780.33398.e4
  29. Zu Y.L., Li C., Ma Z., Li D., Fu X. Roles of CD8+CD28– T regulatory cells in acute infectious mononucleosis in children. Zhongua Er Ke Za Zhi, 2007, vol. 45, no. 3, pp. 208–211.

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Copyright (c) 2021 Balatskaya N.V., Saakyan S.V., Myakoshina E.B., Kulikova I.G., Krichevskaya G.I.

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