New opportunities of immunocorrection in complex treatment of cervical cancer patients

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Abstract

Etiologic role of human papilloma virus in cervical carcinoma is well known so this might be the base of application of interferonogenicimmunomodulators in their complex treatment. Evaluation of the role and place of immunotherapy and immunocorrection in combination treatment is one of the urgent problems in both clinical immunology and oncology. In this study we used one of them – allokin-alpha (alloferon) – together with plasmapheresis which contributes to detoxication and enhancement of the tumor cells` sensitivity to cytostatics in complex treatment of locally advanced cervical cancer patients receiving neoadjuvantpolychemotherapy (NCT). Clinical effect of such treatment was described in our previous studies. The purpose of the present research is to study the effect of the application of immunomodulatorallokin-alpha (A) and plasmapheresis (PP) in complex treatment of cervical cancer patients on their cell-mediated immunity and cytokines` composition in serum. Cervical cancer patients with locally-advanced tumors were divided into two groups. The control one received NCT, the basic one consisted of two subgroups – the 1st one in the course of NCT additionally received procedures of gravitational PP, the 2nd one received NCT, PP and 6 injections of allokin-alpha. Immunological parameters was tested in dynamics by flow cytometry and ELISA. Dynamics of cell-mediated immunity parameters revealed the decrease of CD19+ cells in patients of all the groups, of Treg in both subgroups of the basic group; of lymphocytes, CD3+ and CD8+ cells in patients after NCT + PP; activated CD3+HLA-DR+ cells in patients after NCT + PP + A though the amount of CD8+HLA-DR+ was elevated. When PP was applied CD3+ cells` levels was found to be lower than after additional administration of A. Analysis of the cytokines` levels showed the increase of IL-8 after NCT + PP, but administration of A caused its` decrease. IL-10 level was minimal in patients having received NCT + PP + A. Application of NCT + PP and NCT + PP + A prevented the elevation of inflammatory cytokines` levels (IL-1β and TNFα) which was observed in patients of the control group after the course of neoadjuvant treatment. Such a dynamics of cytokines levels suggests that application of allokin-alpha together with plasmapheresis and neoadjuvant chemotherapy might be useful in complex treatment of cervical cancer patients with locally advanced tumors.

About the authors

A. P. Menshenina

National Medical Research Centre for Oncology

Author for correspondence.
Email: anna.menshenina.00@mail.ru

Menshenina Anna P., PhD (Medicine), Leading Research Associate, Department of Reproductive Tumors

344037, Rostov-on-Don, 14th line, 63

Russian Federation

E. Yu. Zlatnik

National Medical Research Centre for Oncology

Email: elena-zlatnik@mail.ru

Zlatnik Elena Yu., PhD, MD (Medicine), Professor, Chief Research Associate, Laboratory of Tumor Immunophenotyping

Rostov-on-Don

A. B. Sagakyants

National Medical Research Centre for Oncology

Email: asagak@rambler.ru

Sagakyants Aleksandr B., PhD (Biology), Head, Laboratory of Tumor Immunophenotyping

Rostov-on-Don

T. I. Moiseenko

National Medical Research Centre for Oncology

Email: moiseenko48@inbox.ru

Moiseenko Tatiana I., PhD, MD (Medicine), Professor, Chief Research Associate, Department of Reproductive Tumors

Rostov-on-Don

N. D. Ushakova

National Medical Research Centre for Oncology

Email: ndu2000@rambler.ru

Ushakova Natalia D., PhD, MD (Medicine), Professor, Anesthesiologist-Reanimatologist, Department of Anesthesiology and Intensive Care

Rostov-on-Don

E. M. Frantsiyants

National Medical Research Centre for Oncology

Email: super.gormon@yandex.ru

Frantsiyants Elena M., PhD, MD (Biology), Professor, Deputy General Director for Science

Rostov-on-Don

E. V. Verenikina

National Medical Research Centre for Oncology

Email: ekat.veren@yandex.ru

Verenikina Ekaterina V., PhD (Medicine), Head, Department of Oncogynecology

Rostov-on-Don

T. G. Chalabova

National Medical Research Centre for Oncology

Email: rnioi@bk.ru

Chalabova Tatiana G., PhD (Medicine), Oncologist, Consulting and Diagnostic Department

Rostov-on-Don

References

  1. Бережная Н.М., Чехун В.Ф. Иммунология злокачественного роста. К.: Наукова думка, 2005. 792 c.
  2. Кит О.И., Златник Е.Ю., Никипелова Е.А., Новикова И.А., Бахтин А.В., Селютина О.Н. Взаимоотношения плоидности и параметров локального иммунитета при опухолях толстой кишки // Молекулярная медицина, 2016. № 1. С. 26-30.
  3. Ковалева О.В., Ефремов Г.Д., Михайленко Д.С., Алексеев Б.Я., Грачев А.Н. Роль макрофагов, ассоциированных с опухолью, в патогенезе почечно-клеточного рака // Онкоурология, 2017. Т. 13, № 1. С. 20-26.
  4. Ковчур П.И., Курмышкина О.В., Волкова Т.О., Бахидзе Е.В. Иммунологические и молекулярногенетические аспекты рака шейки матки до и после лечения. Петрозаводск: ПетрГУ. [Электронный ресурс]: научное электронное издание. 1 электрон. опт. диск (CD-ROM). 2017.
  5. Ковчур П.И., Олейник Е.К., Бахлаев И.Е, Чуров А.В, Олейник В.М. Клиническая эффективность «аллокина-альфа» и его влияние на эксперессию маркеров регуляторных лимфоцитов Treg при лечении больных с хронической ВПЧ-инфекцией // Материалы 10 Всероссийского научного форума «Мать и дитя» 30 июня – 2 июля 2009. М.: МЕДИ Экспо, 2009. С. 127.
  6. Короленкова Л.И. Снижение вирусной нагрузки, определенной методом гибридного захвата, у больных тяжелыми интраэпителиальными неоплазиями шейки матки, как результат эффективной предэксцизионной терапии аллокином-альфа // Акушерство и гинекология, 2012. № 4/2. С. 78-82.
  7. Лепик К.В. Ингибиторы иммунных контрольных точек в терапии лимфом // Клиническая онкогематология, 2018. Т. 11, № 4. С. 303-312.
  8. Меньшенина А.П., Моисеенко Т.И., Франциянц Е.М., Ушакова Н.Д., Назаралиева Н.А. Сравнительная оценка различных модификаций предоперационной полихимиотерапии у больных местнораспространенным раком шейки матки // Фундаментальные исследования, 2015. № 1-8. С. 1629-1633.
  9. Неродо Г.А., Ушакова Н.Д., Горошинская И.А., Мкртчян Э.Т., Меньшенина А.П. Применение плазмафереза в комплексном лечении распространенного рака яичников III-IV стадий // Известия высших учебных заведений. Северо-Кавказский регион. Естественные науки, 2014. № 1. С. 98-102.
  10. Перельмутер В.М., Таширева Л.А., Манских В.Н., Денисов Е.В., Савельева О.Е., Кайгородова Е.В., Завьялова М.В. Иммуновоспалительные реакции в микроокружении гетерогенны, пластичны, определяют противоопухолевый эффект или агрессивное поведение опухоли // Журнал общей биологии, 2017. Т. 78, № 5. С. 15-36.
  11. Ушакова Н.Д., Неродо Г.А., Горошинская И.А., Златник Е.Ю., Мкртчян Э.Т., Меньшенина А.П. Оценка эффективности плазмафереза в лечении больных раком яичников // Российский медицинский журнал, 2014. № 3. С. 21-26.
  12. Bae S., Oh K., Kim H., Kim Y., Kim H.R., Hwang Y.I., Lee D.S., Kang J.S., Lee W.J. The effect of alloferon on the enhancement of NK cell cytotoxicity against cancer via the up-regulation of perforin/granzyme B secretion. Immunobiology, 2013, Vol. 218, no. 8, pp. 1026-1033.
  13. Bambauer R., Latzo R., Schiel R. Therapeutic plasma exchange and selective plasma separation methods. Fundamental technologies, pathology and clinical results. Pabst, Wolfgang Science, 2013, pp. 395-402.
  14. Beyer M., Schultze J.L. Regulatory T cells in cancer. Blood, 2006, Vol. 108, no. 3, рр. 804-811.
  15. Chernysh S., Kozuharova I., Artsibasheva I. Anti-tumor activity of immunomodulatory peptide alloferon-1 in mouse tumor transplantation model. Int. Immunopharmacol., 2012, Vol. 12, no. 1, pp. 312-314.
  16. Curiel T.J., Coukos G., Zou L. Specific recruitment of regulatory T-cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat. Med., 2004, no. 10, pp. 942-949.
  17. Hodi F.S., O’Day S.J., McDermott D.F. Improved survival with ipilimumab in patients with metastatic melanoma. N. Engl. J. Med., 2010, Vol. 363, no. 8, pp. 711-723.
  18. Jee Y.S., Jang T.J., Jung K.H. Prostaglandin E2 and Interleukin-1β reduce E-cadherin expression by enhancing snail expression in gastric cancer cells. J. Korean Med. Sci., 2012, Vol. 27, pp. 987-992.
  19. Kono K., Kawada H., Takahashi A., Sugai H., Mimura K., Miyagawa N., Omata H., Fujii H. CD4+CD25high regulatory T cells increase with tumor stage in patients with gastric and esophageal cancers. Cancer Immunol. Immunother., 2006, Vol. 55, no. 9, pp. 1064-1071.
  20. Müerköster S., Wegehenkel K., Arlt A., Witt M., Sipos B., Kruse M.-L., Sebens T., Klöppel G., Kalthoff H., Fölsch U.R., Schäfer H. Tumor stroma interactions induce chemoresistance in pancreatic ductal carcinoma cells involving increased secretion and paracrine effects of nitric oxide and interleukin-1beta. Cancer Res., 2004, Vol. 64, no. 4, pp. 1331-1337.
  21. Mulder K.C.L., Lima L.A., Miranda V.J., Dias S.C., Franco O.L. Current scenario of peptide-based drugs: the key roles of cationic antitumor and antiviral peptides. Front. Microbiol., Vol. 4, 321. doi: 10.3389/fmicb.2013.00321.
  22. Pardoll D.M. The blockade of immune checkpoints in cancer immunotherapy. Nat. Rev. Cancer, 2012, Vol. 12, no. 4, pp. 252-264.
  23. Robert C., Schachter J., Long G.V. Pembrolizumab versus ipilimumab in advanced melanoma. N. Engl. J. Med., 2015, Vol. 372, no. 26, рр.2521-2532.
  24. Spill F., Reynolds D.S., Kamm R.D., Zaman M.H. Impact of the physical microenvironment on tumor progression and metastasis. Curr. Opin. Biotechnol., 2016, Vol. 40, pp. 41-48.
  25. Thornton A.M., Donovan E.E., Piccirillo C.A., Shevach E.M. Cutting edge: IL-2 is critically required for the in vitro activation of CD4+CD25+ T cell suppressor function. J. Immunol., 2004, no. 172, pp. 6519-6523.
  26. Wu S.T., Sun G.H., Hsu C.Y., Huang C.S., Wu Y.H., Wang H.H., Sun K.H. Tumor necrosis factor-α induces epithelial-mesenchymal transition of renal cell carcinoma cells via a nuclear factor kappa B-independent mechanism. Exp. Biol. Med. (Maywood), 2011, Vol. 236, pp. 1022-1029.
  27. Wu Y., Deng J., Rychahou P.G., Qiu S., Evers B.M., Zhou B.P. Stabilization of snail by NF-kappaB is required for inflammation-induced cell migration and invasion. Cancer Cell, 2009, Vol. 15, pp. 416-428.

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Copyright (c) 2021 Menshenina A.P., Zlatnik E.Y., Sagakyants A.B., Moiseenko T.I., Ushakova N.D., Frantsiyants E.M., Verenikina E.V., Chalabova T.G.

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