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PHENOTYPIC FEATURES AND CHEMILUMINESCENT ACTIVITY OF NEUTROPHILIC GRANULOCYTES IN THE PATIENTS WITH RENAL CANCER

https://doi.org/10.15789/1563-0625-2016-3-259-268

Abstract

The aim of our study was to investigate the relationship between phenotype and «respiratory burst» activity of neutrophilic granulocytes in patients with renal cancer. The study included 73 patients with renal cell carcinoma (T3N0M0, clear-cell type) before surgical treatment at the age of 40-55 years. The diagnosis of renal cancer was histologically verified in all the patients. Fifty healthy age-matched persons were involved as a control group. Phenotyping of blood neutrophilic granulocytes was performed by flow cytometry. The respiratory burst in blood neutrophilic granulocytes was evaluated using spontaneous and zymosan-induced luminol- and lucigenin-dependent chemiluminescence. Some changes in relationships between the phenotypic indicators of neutrophils and «respiratory burst» were detected in patients with renal cancer. The patients exhibited a loss of relationship between induction of primary and secondary reactive oxygen species, and numbers of CD11b+, CD62L+, and CD64+ neutrophils. These correlations are detected with HLA-DR+ cell levels, like in control group. The patients’ samples showed a correlation between the superoxide radical synthesis by resting neutrophils, and CD62L expression. These relationships disappear when assessing antigen-induced «respiratory burst» response. The correlations between primary and secondary reactive oxygen species, and the numbers of 
CD11b+, CD62L+ and CD64+ neutrophils found in healthy people characterize a positive relationship between the «respiratory burst» indexes and activation of cells as reflected by expression of adhesive and functional receptors. It may be assumed that altered relationship between the «respiratory burst» indicators and neutrophil phenotype in the patients with renal cell carcinoma is determined by various factors. Firstly, cancer-associated phenotypic changes of blood neutrophils (decreased content of CD11b+, CD62L+, CD64+, HLA-DR+, and HLA-DR+ CD64+ neutrophils, increased expression of CD16, and HLA-DR receptors) thus, possibly, being connected with intra-tumor migration of the cells. Secondly, the patients show an increase in «respiratory burst» intensity in neutrophils, due to enhanced synthesis of primary and secondary reactive oxygen species, which may be connected to the action of various tumor factors (antigens, regulatory molecules).
The relationships revealed between phenotype and «respiratory burst» of neutrophils may specifically characterize immunopathogenesis of kidney cancer and can be used in development of immunotherapeutic approaches aiming to stimulate anti-tumor activity of phagocytic cells.

About the Authors

A. A. Savchenko
Research Institute of Medical Problems of the North, Krasnoyarsk, Russian Federation Krasnoyarsk State V.F. Voino-Yasenetsky Medical University, Krasnoyarsk, Russian Federation
Russian Federation

PhD, MD (Medicine), Professor, Head, Laboratory of Molecular and Cellular Physiology and Pathology



A. G. Borisov
Research Institute of Medical Problems of the North, Krasnoyarsk, Russian Federation Krasnoyarsk State V.F. Voino-Yasenetsky Medical University, Krasnoyarsk, Russian Federation
Russian Federation

PhD (Medicine), Leading Research Associate, Laboratory of Molecular and Cellular Physiology and Pathology



A. A. Modestov
Krasnoyarsk Regional A.I. Kryzhanovsky Center of Clinical Oncology, Krasnoyarsk, Russian Federation
Russian Federation
PhD (Medicine), Chief Physician


I. V. Kudryavtsev
Institute of Experimental Medicine, St. Petersburg, Russian Federation Far Eastern Federal University, Krasnoyarsk, Russian Federation Pavlov First St. Petersburg State Medical University, St. Petersburg, Russian Federation
Russian Federation

197376, Russian Federation, St. Petersburg, Acad. Pavlov str., 12. Phone: 7 (812) 234-29-29 PhD (Medicine), Senior Research Associate, Institute of Experimental Medicine



A. V. Moshev
Research Institute of Medical Problems of the North, Krasnoyarsk, Russian Federation
Russian Federation

Junior Research Associate, Laboratory of Molecular and Cellular Physiology and Pathology



I. I. Gvozdev
Research Institute of Medical Problems of the North, Krasnoyarsk, Russian Federation
Russian Federation

Junior Research Associate, Laboratory of Molecular and Cellular Physiology and Pathology



O. G. Tonacheva
Krasnoyarsk Regional A.I. Kryzhanovsky Center of Clinical Oncology, Krasnoyarsk, Russian Federation
Russian Federation
Head of Department


References

1. Алексеев Б.Я., Анжиганова Ю.В., Лыков А.В., Леонов О.В., Варламов С.А., Горбачев А.Л., Магер В.О., Демичева Н.Н., Мишугин С.В., Зырянов А.В., Карнаух П.А., Никитин Р.В. Особенности диагностики и лечения рака почки в России: предварительные результаты многоцентрового кооперированного исследования // Онкоурология, 2012. № 3. С. 24-31. [Alekseev B.Ya., Anzhiganova Yu.V., Lykov A.V., Leonov O.V., Varlamov S.A., Gorbachev A.L., Mager V.O., Demicheva N.N., Mishugin S.V., Zyryanov A.V., Karnauh P.A., Nikitin R.V. Features of diagnosis and treatment of kidney cancer in Russia: preliminary results of a multicenter cooperative study. Onkourologiya = Oncourology, 2012, no. 3, pp. 24-31. (In Russ.)]

2. Владимиров Ю.А., Проскурина Е.В. Свободные радикалы и клеточная хемилюминесценция // Успехи биологической химии, 2009. T. 49. C. 341-388. [Vladimirov Yu.A., Proskurina E.V. Free radicals and cellular chemiluminescence. Uspekhi biologicheskoy khimii = Advances of Biological Chemistry, 2009, Vol. 49, pp. 341-38. (In Russ.)]

3. Коленчукова О.А., Савченко А.А., Смирнова С.В. Особенности люминол- и люцигенин-зависимой хемилюминесценции нейтрофильных гранулоцитов у больных хроническим риносинуситом // Медицинская иммунология, 2010. Т. 12, № 4-5. С. 437-440. [Kolenchukova O.A., Savchenko A.A., Smirnova S.V. The luminol- and lucigenin-dependent chemiluminescence features of neutrophils in patients with chronic rhinosinusitis. Meditsinskaya immunologiya = Medical Immunology (Russia), 2010, Vol. 12, no. 4-5, pp. 437-440. (In Russ.)] http://dx.doi.org/10.15789/1563-0625-2010-4-5-437-440

4. Куртасова Л.М., Савченко А.А., Шкапова Е.А. Клинические аспекты функциональных нарушений нейтрофильных гранулоцитов при онкопатологии. Новосибирск: Наука, 2009. 184 с. [Kurtasova L.M., Savchenko A.A., Shkapova E.A. Clinical aspects of neutrophil granulocytes functional disorders in cancer pathology]. Novosibirsk: Nauka, 2009. 184 p.

5. Мальцева В.Н., Авхачева Н.В., Сафронова В.Г. Общие закономерности в изменениях функциональной активности нейтрофилов при росте in vivo опухолей разной иммуногенности // Бюллетень экспериментальной биологии и медицины, 2010. Т. 150, № 11. С. 520-523. [Mal’tseva V.N., Avkhacheva N.V., Safronova V.G. Common regularities in changes of the neutrophil functional activity during in vivo growth of tumors of different immunogenic activity. Byulleten` eksperimental`noy biologii i meditsiny = Bulletin of Experimental Biology and Medicine, 2010, Vol. 150, no. 11, pp. 520-523. (In Russ.)]

6. Мальцева В.И., Сафронова В.Г. Неоднозначность роли нейтрофила в генезе опухоли // Цитология, 2009. Т. 51, № 6. С. 467-474. [Mal’tseva V.N., Safronova V.G. Ambiguity role of neutrophils in oncogenesis. Tsitologiya = Cytology, 2009, Vol. 51, no. 6, pp. 467-474. (In Russ.)]

7. Носов Д.А., Ворошилова Е.А., Саяпина М.С. Иммунотерапия при метастатическом раке почки: ее роль на современном этапе и перспективы клинического использования // Онкоурология, 2013. № 3. С. 37-42. [Nosov D.A., Voroshilova E.A., Sajapina M.S. Immunotherapy for metastatic kidney cancer: its role at the current stage and prospects of clinical application. Onkourologiya = Oncourology, 2013, no. 3, pp. 37-42. (In Russ.)]

8. Савченко А.А., Здзитовецкий А.Г., Борисов А.Г., Лузан Н.А. Хемилюминесцентная и энзиматическая активность нейтрофильных гранулоцитов у больных распространенным гнойным перитонитом в зависимости от исхода заболевания // Вестник РАМН. 2014. № 5-6. С. 23-28. [Savchenko A.A., Zdzitovetskiy D.E., Borisov A.G., Luzan N.A. Chemiluminescent and enzyme activity of neutrophils in patients with widespread purulent peritonitis depending on the outcome of disease. Vestnik RAMN = Annals of the Russian Academy of Medical Sciences, 2014, no. 5-6, pp. 23-28 (In Russ.)]

9. Хайдуков С.В., Байдун Л.А., Зурочка А.В., Тотолян Арег А. Стандартизованная технология «Исследование субпопуляционного состава лимфоцитов периферической крови с применением проточных цитофлюориметров-анализаторов» (Проект) // Медицинская иммунология, 2012. Т. 14, № 3. С. 255-268. [Khaydukov S.V., Baydun L.A., Zurochka A.V., Totolian Areg A. Standardized technology «Research of lymphocytes subpopulation composition in peripheral blood using flow cytometry analyzers» (Draft). Meditsinskaya immunologiya = Medical Immunology (Russia), 2012, Vol. 14, no. 3, pp. 255-268. (In Russ.)] http://dx.doi.org/10.15789/1563-0625-2012-3-255-268

10. Шкапова Е.А., Куртасова Л.М., Савченко А.А. Показатели люцигенин- и люминолзависимой хемилюминесценции нейтрофилов крови у больных раком почки // Бюллетень экспериментальной биологии и медицины, 2010. Т. 149, № 2. С. 201-203. [Shkapova E.A., Kurtasova L.M., Savchenko A.A. Lucigenin- and luminoldependent chemiluminescence of blood neutrophils in patients with renal cancer. Byulleten` eksperimental`noy biologii i meditsiny = Bulletin of Experimental Biology and Medicine, 2010, Vol. 149, no. 2. pp. 201-203 (In Russ.)]

11. Bayat B., Tjahjono Y., Berghцfer H., Werth S., Deckmyn H., De Meyer S.F., Sachs U.J., Santoso S. Choline Transporter-Like Protein-2: New von Willebrand Factor-Binding Partner Involved in Antibody-Mediated Neutrophil Activation and Transfusion-Related Acute Lung Injury. Arterioscler. Thromb. Vasc. Biol., 2015, Vol. 35, no. 7, pp. 1616-1622.

12. Braster R., O’Toole T., van Egmond M. Myeloid cells as effector cells for monoclonal antibody therapy of cancer. Methods, 2014, Vol. 65, no. 1, pp. 28-37.

13. Cortez-Retamozo V., Etzrodt M., Newton A., Rauch P.J., Chudnovskiy A., Berger C., Ryan R.J., Iwamoto Y., Marinelli B., Gorbatov R., Forghani R., Novobrantseva T.I., Koteliansky V., Figueiredo J.L., Chen J.W., Anderson D.G., Nahrendorf M., Swirski F.K., Weissleder R., Pittet M.J. Origins of tumor-associated macrophages and neutrophils. Proc. Natl. Acad. Sci. USA, 2012, Vol. 109, no. 7, pp. 2491-2496.

14. Finisguerra V., Di Conza G., Di Matteo M., Serneels J., Costa S., Thompson A.A., Wauters E., Walmsley S., Prenen H., Granot Z., Casazza A., Mazzone M. MET is required for the recruitment of anti-tumoural neutrophils. Nature, 2015, Vol. 522, no. 7556, pp. 349-353.

15. Fossati G., Moots R.J., Bucknall R.C., Edwards S.W. Differential role of neutrophil Fcgamma receptor IIIB (CD16) in phagocytosis, bacterial killing, and responses to immune complexes. Arthritis Rheum., 2002, Vol. 46, no. 5, pp. 1351-1361.

16. Legitimo A., Consolini R., Failli A., Orsini G., Spisni R. Dendritic cell defects in the colorectal cancer. Hum. Vaccin Immunother., 2014, Vol. 10, no. 11, pp. 3224-3235.

17. Li P., Znaor A., Holcatova I., Fabianova E., Mates D., Wozniak M.B., Ferlay J., Scelo G. Regional geographic variations in kidney cancer incidence rates in European countries. Eur. Urol., 2015, Vol. 67, no. 6, pp. 1134-1141.

18. Lucca I., Klatte T., Fajkovic H., de Martino M., Shariat S.F. Gender differences in incidence and outcomes of urothelial and kidney cancer. Nat. Rev. Urol., 2015, Vol. 12, no. 10, pp. 585-592.

19. Luider J., Cyfra M., Johnson P., Auer I. Impact of the new Beckman Coulter Cytomics FC 500 5-color flow cytometer on a regional flow cytometry clinical laboratory service. Lab. Hematol., 2004, Vol. 10, pp. 102-108.

20. Maecker H., McCoy P., Nussenblatt R. Standardizing immunophenotyping for the human immunology project. Nat. Rev. Immunol., 2012, Vol. 12, pp. 191-200.

21. Mancardi D.A., Albanesi M., Jönsson F., Iannascoli B., Van Rooijen N., Kang X., England P., Daлron M., Bruhns P. The high-affinity human IgG receptor FcγRI (CD64) promotes IgG-mediated inflammation, anaphylaxis, and antitumor immunotherapy. Blood, 2013, Vol. 121, no. 9, pp. 1563-1573.

22. Mantia-Smaldone G.M., Chu C.S. A review of dendritic cell therapy for cancer: progress and challenges. BioDrugs, 2013, Vol. 27, no. 5, pp. 453-468.

23. Mastej K., Adamiec R. Neutrophil surface expression of CD11b and CD62L in diabetic microangiopathy. Acta Diabetol., 2008, Vol. 45, no. 3, pp. 183-190.

24. O’Hare F.M., Watson W., O’Neill A., Grant T., Onwuneme C., Donoghue V., Mooney E., Downey P., Murphy J., Twomey A., Molloy E.J. Neutrophil and monocyte toll-like receptor 4, CD11b and reactive oxygen intermediates, and neuroimaging outcomes in preterm infants. Pediatr. Res., 2015, Vol. 78, no. 1, pp. 82-90.

25. Pauken K.E., Wherry E.J. Overcoming T cell exhaustion in infection and cancer. Trends Immunol., 2015, Vol. 36, no. 4, pp. 265-276.

26. Perri S.R., Martineau D., Francois M., Lejeune L., Bisson L., Durocher Y., Galipeau J. Plasminogen Kringle 5 blocks tumor progression by antiangiogenic and proinflammatory pathways. Mol. Cancer Ther., 2007, Vol. 6, no. 2, pp. 441-449.

27. Rymaszewski A.L., Tate E., Yimbesalu J.P., Gelman A.E., Jarzembowski J.A., Zhang H., Pritchard K.A.Jr., Vikis H.G. The role of neutrophil myeloperoxidase in models of lung tumor development. Cancers (Basel), 2014, Vol. 6, no. 2, pp. 1111-1127.

28. Sarode S.C., Sarode G.S. Neutrophil-tumor cell cannibalism in oral squamous cell carcinoma. J. Oral Pathol. Med., 2014, Vol. 43, no. 6, pp. 454-458.

29. Swierczak A., Mouchemore K.A., Hamilton J.A., Anderson R.L. Neutrophils: important contributors to tumor progression and metastasis. Cancer Metastasis Rev., 2015, Vol. 34, pp. 735-751.

30. Verschoor C.P., Loukov D., Naidoo A., Puchta A., Johnstone J., Millar J., Lelic A., Novakowski K.E., Dorrington M.G., Loeb M., Bramson J.L., Bowdish D.M. Circulating TNF and mitochondrial DNA are major determinants of neutrophil phenotype in the advanced-age, frail elderly. Mol. Immunol., 2015, Vol. 65, no. 1, pp. 148-156.

31. Whiteside T.L. Regulatory T cell subsets in human cancer: are they regulating for or against tumor progression? Cancer Immunol. Immunother., 2014, Vol. 63, no. 1, p. 67-72.


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For citations:


Savchenko A.A., Borisov A.G., Modestov A.A., Kudryavtsev I.V., Moshev A.V., Gvozdev I.I., Tonacheva O.G. PHENOTYPIC FEATURES AND CHEMILUMINESCENT ACTIVITY OF NEUTROPHILIC GRANULOCYTES IN THE PATIENTS WITH RENAL CANCER. Medical Immunology (Russia). 2016;18(3):259-268. (In Russ.) https://doi.org/10.15789/1563-0625-2016-3-259-268

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