Preview

Medical Immunology (Russia)

Advanced search

PHENOTYPIC PECULIARITIES OF DENDRITIС CELLS DIFFERENTIATED FROM BLOOD MONOCYTES IN PATIENTS WITH KIDNEY CANCER

https://doi.org/10.15789/1563-0625-2018-2-215-226

Abstract

The aim of the study was to investigate the phenotypic features of dendritic cell (DCs) differentiated from peripheral blood monocytes in patients with kidney cancer (KC). The study involved 28 patients with KC (Т3N0М0, clear cell type) before surgical treatment at the age of 40-55 years and 31 healthy age-matched people. Immature DCs (IDCs) were generated from blood monocytes by culturing for 5 days with GM-CSF and IFNα. Activation of the DCs (MDCs) was induced by incubation with tumor cell lysate and TNFα followed by incubation for 48 hours. Phenotyping of DCs at different maturity degrees was carried out by the method of flow cytometry. It was found that the monocytes differentiated into IDCs formed a cellular pool with a high level of costimulatory activity in patients with KC, by increasing number of cells with a high level of CD80 and CD86 receptor expression. In this case, a significant amount of undifferentiated monocytes and cells with an intermediate phenotype (CD14+CD83+) remained in the cell culture. In KC patients, the cell culture formed an increased number of IDCs with the CD83+CD80highCD86highHLA-DR+ phenotype (in comparison with the control values). However, expression level of the HLA-DR receptor on CD83+CD80highCD86high-IDCs in patients with KC was reduced. Therefore, this type of DCs has a high costimulatory and weak antigen-presenting activity. Maturation (activation) of DCs from patients with KC was accompanied by retained amounts of undifferentiated monocytes in cell culture associated with decreased contents of cells with CD14+CD83+ phenotype. Presumably, a part of cells with the CD14+CD83+ phenotype and additional antigenic and cytokine load matured to the level of MDCs. Mature DCs in patients with KC are characterized by weak costimulatory and antigen presenting activity, due to decreased expression of CD83 and CD86 markers. Upon maturation, the amount of DCs with different levels of CD80 expression in cell culture in healthy people and in patients with RP is equalized, but the MDCs with a highly active phenotype (CD83+CD80highCD86high и CD83+CD80highCD86highHLA-DR+) are formed with KC cells to lesser degree. Moreover, MDCs with CD83+CD80highCD86high phenotype in tumor patients show weaker expression of receptors providing costimulatory and antigen-presenting activity. The differences in the IDCs and MDCs phenotype between healthy people and KC patients may be determined by different features of phenotype and functional activity in blood monocyte populations as well as immunosuppressive factors synthesized by the tumor.

About the Authors

A. A. Savchenko
Research Institute of Medical Problems of the North, Krasnoyarsk Research Center, Siberian Branch, Russian Academy of Sciences; Krasnoyarsk V.F. Voino-Yasenetsky State Medical University
Russian Federation

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

Head, Department of Physiology



A. G. Borisov
Research Institute of Medical Problems of the North, Krasnoyarsk Research Center, Siberian Branch, Russian Academy of Sciences; Krasnoyarsk V.F. Voino-Yasenetsky State Medical University
Russian Federation

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

Assistant Professor, Department of Infections



I. V. Kudryavtsev
Research Institute of Experimental Medicine; Far Eastern Federal University; First St. Petersburg State I. Pavlov Medical University, Department оf Immunology
Russian Federation

PhD (Biology) Senior Research Associate

Department оf Immunology

197376, Russian Federation, St. Petersburg, Acad. Pavlov str., 12. Phone: 7 (812) 234-29-29



I. I. Gvozdev
Research Institute of Medical Problems of the North, Krasnoyarsk Research Center, Siberian Branch, Russian Academy of Sciences
Russian Federation
Junior Research Associate, Laboratory of Molecular and Cellular Physiology and Pathology, Laboratory of Molecular and Cellular Physiology and Pathology


A. V. Moshev
Research Institute of Medical Problems of the North, Krasnoyarsk Research Center, Siberian Branch, Russian Academy of Sciences
Russian Federation
Junior Research Associate, Laboratory of Molecular and Cellular Physiology and Pathology, Laboratory of Molecular and Cellular Physiology and Pathology


References

1. Кескинов А.А., Щурин М.Р., Бухман В.М., Шпрах З.С. Влияние секретируемых опухолью веществ на дендритные клетки при раке // Российский биотерапевтический журнал, 2017. Т. 16, № 1. С. 12-23. [Keskinov A.A., Shhurin M.R., Buhman V.M., Shprah Z.S. Impact of tumor-derived factors on dendritic cells in cancer. Rossiyskiy bioterapevticheskiy zhurnal = Russian Biotherapeutic Journal, 2017, Vol. 16, no. 1, pp. 12-23. (In Russ.)]

2. Кудрявцев И.В., Субботовская А.И. Опыт измерения параметров иммунного статуса с использованием шести-цветного цитофлуоримерического анализа // Медицинская иммунология, 2015. Т. 17, № 1. С. 19-26. [Kudryavtsev I.V., Subbotovskaya A.I. Application of six-color flow cytometric analysis for immune profile monitoring. Meditsinskaya immunologiya = Medical Immunology (Russia), 2015, Vol. 17, no. 1, pp. 19-26. (In Russ.)] doi: 10.15789/1563-0625-2015-1-19-26.

3. Леплина О.Ю., Тихонова М.А., Тыринова Т.В., Алямкина Е.А., Богачев С.С., Останин А.А., Черных Е.Р. Функциональная активность IFNα- и IL-4-индуцированных дендритных клеток человека: сравнительное исследование // Медицинская иммунология, 2014. Т. 16, № 1. С. 43-52. [Leplina O.Yu., Tikhonova M.A., Tyrinova T.V., Alyamkina E.A., Bogachev S.S., Ostanin A.A., Chernykh E.R. Functional activity of IFNα- and IL-4- induced human dendritic cells: a comparative study. Meditsinskaya immunologiya = Medical Immunology (Russia), 2014, Vol. 16, no. 1, pp. 43-52. (In Russ.)] doi: 10.15789/1563-0625-2014-1-43-52.

4. Савченко А.А., Борисов А.Г., Модестов А.А., Мошев А.В., Кудрявцев И.В., Тоначева О.Г., Кощеев В.Н. Фенотипический состав и хемилюминесцентная активность моноцитов у больных почечноклеточным раком // Медицинская иммунология, 2015. Т. 17, № 2. С. 141-150. [Savchenko A.A., Borisov A.G., Modestov A.A., Moshev A.V., Kudryavtsev I.V., Tonacheva O.G., Koshcheev V.N. Monocytes subpopulations and chemiluminescent activity in patients with renal cell carcinoma. Meditsinskaya immunologiya = Medical Immunology (Russia), 2015, Vol. 17, no. 2, pp. 141-150. (In Russ.)] doi:10.15789/1563-0625-2015-2-141-150.

5. Савченко А.А., Модестов А.А., Мошев А.В., Тоначева О.Г., Борисов А.Г. Цитометрический анализ NK- и NKT-клеток у больных почечноклеточным раком // Российский иммунологический журнал, 2014. Т. 8 (17), № 4. С. 1012-1018. [Savchenko A.A., Modestov A.A., Moshev A.V., Tonacheva O.G., Borisov A.G. Cytometric analysis of NK- and NKT-cells in patients with renal cell carcinoma. Rossiyskiy immunologicheskiy zhurnal = Russian Immunological Journal, 2014, Vol. 8 (17), no. 4, pp. 1012-1018. (In Russ.)]

6. Bari R., Hartford C., Chan W.K., Vong Q., Li Y., Gan K., Zhou Y., Cheng C., Kang G., Shurtleff S., Turner V., Pui C.H., Downing J.R., Leung W. Genome-wide single-nucleotide polymorphism analysis revealed SUFU suppression of acute graft-versus-host disease through downregulation of HLA-DR expression in recipient dendritic cells. Sci. Rep., 2015, Vol. 5, p. 11098.

7. Battaglia S., Muhitch J.B. Unmasking targets of antitumor immunity via high-throughput antigen profiling. Curr. Opin. Biotechnol., 2016, Vol. 42, pp. 92-97.

8. Ciudad M.T., Sorvillo N., van Alphen F.P., Catalán D., Meijer A.B., Voorberg J., Jaraquemada D. Analysis of the HLA-DR peptidome from human dendritic cells reveals high affinity repertoires and nonconventional pathways of peptide generation. J. Leukoc. Biol., 2017, Vol. 101, no. 1, pp. 15-27.

9. da Cunha A., Antoniazi Michelin M., Cândido Murta E.F. Phenotypic profile of dendritic and T cells in the lymph node of Balb/C mice with breast cancer submitted to dendritic cells immunotherapy. Immunol. Lett., 2016, Vol. 177, pp. 25-37.

10. Di Pucchio T., Lapenta C., Santini S.M., Logozzi M., Parlato S., Belardelli F. CD2+/CD14+ monocytes rapidly differentiate into CD83+ dendritic cells. Eur. J. Immunol., 2003, Vol. 33, no. 2, pp. 358-367.

11. Gardner A., Ruffell B. Dendritic cells and cancer immunity. Trends Immunol., 2016, Vol. 37, no. 12, pp. 855-865.

12. Grange C., Tapparo M., Tritta S., Deregibus M.C., Battaglia A., Gontero P., Frea B., Camussi G. Role of HLA-G and extracellular vesicles in renal cancer stem cell-induced inhibition of dendritic cell differentiation. BMC Cancer, 2015, Vol. 15, p. 1009.

13. Jakubzick C.V., Randolph G.J., Henson P.M. Monocyte differentiation and antigen-presenting functions. Nat. Rev. Immunol., 2017, Vol. 17, no. 6, pp. 349-362.

14. Jia J., Wang Z., Li X., Wang Z., Wang X. Morphological characteristics and co-stimulatory molecule (CD80, CD86, CD40) expression in tumor infiltrating dendritic cells in human endometrioid adenocarcinoma. Eur. J. Obstet. Gynecol. Reprod. Biol., 2012, Vol. 160, no. 2, pp. 223-227.

15. Wang Y. Immune tolerance of mice allogenic tooth transplantation induced by immature dendritic cells. Int. J. Clin. Exp. Med., 2015, Vol. 8, no. 4, pp. 5254-5262.

16. Liu W.H., Liu J.J., Wu J., Zhang L.L., Liu F., Yin L., Zhang M.M., Yu B. Novel mechanism of inhibition of dendritic cells maturation by mesenchymal stem cells via interleukin-10 and the JAK1/STAT3 signaling pathway. PLoS ONE, 2013, Vol. 8, no. 1, e55487. doi: 10.1371/journal.pone.0055487.

17. Luider J.1., 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.

18. Macri C., Dumont C., Johnston A.P., Mintern J.D. Targeting dendritic cells: a promising strategy to improve vaccine effectiveness. Clin. Transl. Immunology, 2016, Vol. 5, no. 3, p. e66.

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

20. Maglioco A., Machuca D.G., Badano M.N., Nannini P., Camerano G.V., Costa H., Meiss R., Ruggiero R.A., Giordano M., Dran G.I. B cells inhibit the antitumor immunity against an established murine fibrosarcoma. Oncol. Lett., 2017, Vol. 13, no. 5, pp. 3225-3232.

21. Ni Y.H., Wang Z.Y., Huang X.F., Shi P.H., Han W., Hou Y.Y., Hua Z.C., Hu A.Q. Effect of siRNA-mediated downregulation of VEGF in Tca8113 cells on the activity of monocyte-derived dendritic cells. Oncol. Lett., 2012, Vol. 3, no. 4, pp. 885-892.

22. Okamoto M., Kobayashi M., Yonemitsu Y., Koido S., Homma S. Dendritic cell-based vaccine for pancreatic cancer in Japan. World J. Gastrointest. Pharmacol. Ther., 2016, Vol. 7, no. 1, pp. 133-138.

23. Oreshkova N., Wichgers Schreur P.J., Spel L., Vloet R.P., Moormann R.J., Boes M., Kortekaas J. Nonspreading rift valley fever virus infection of human dendritic cells results in downregulation of CD83 and full maturation of bystander cells. PLoS ONE, 2015, Vol. 10, no. 11, e0142670. doi: 10.1371/journal.pone.0142670.

24. Pfirschke C., Siwicki M., Liao H.W., Pittet M.J. Tumor microenvironment: no effector T сells without dendritic cells. Cancer Cell, 2017, Vol. 31, no. 5, pp. 614-615.

25. Prechtel A.T., Steinkasserer A. CD83: an update on functions and prospects of the maturation marker of dendritic cells. Arch. Dermatol. Res., 2007, Vol. 299, no. 2, pp. 59-69.

26. Reardon D.A., Mitchell D.A. The development of dendritic cell vaccine-based immunotherapies for glioblastoma. Semin. Immunopathol., 2017, Vol. 39, no. 2, pp. 225-239.

27. Seyfizadeh N., Muthuswamy R., Mitchell D.A., Nierkens S., Seyfizadeh N. Migration of dendritic cells to the lymph nodes and its enhancement to drive anti-tumor responses. Crit. Rev. Oncol. Hematol., 2016, Vol. 107, pp. 100-110.

28. Tan P., He L., Han G., Zhou Y. Optogenetic immunomodulation: shedding light on antitumor immunity. Trends Biotechnol., 2017, Vol. 35, no. 3, pp. 215-226.

29. Veglia F., Gabrilovich D.I. Dendritic cells in cancer: the role revisited. Curr. Opin. Immunol., 2017, Vol. 45, pp. 43-51.

30. Xie J., Lin Y.K., Wang K., Che B., Li J.Q., Xu X., Han F., Liang D.H. Induced immune tolerance of autoantigen loaded immature dendritic cells in homogenic lupus mice. Genet. Mol. Res., 2014, Vol. 13, no. 1, pp. 1251-1262.

31. Yan F., Cai L., Hui Y., Chen S., Meng H., Huang Z. Tolerogenic dendritic cells suppress murine corneal allograft rejection by modulating CD28/CTLA-4 expression on regulatory T cells. Cell. Biol. Int., 2014, Vol. 38, no. 7, pp. 835-848.

32. Zhang H., Xie Y., Li W., Chibbar R., Xiong S., Xiang J. CD4(+) T cell-released exosomes inhibit CD8(+) cytotoxic T-lymphocyte responses and antitumor immunity. Cell. Mol. Immunol., 2011, Vol. 8, no. 1, pp. 23-30.

33. Zhang L., Xia C.Q. PD-1/PD-L1 Interaction maintains allogeneic immune tolerance induced by administration of ultraviolet B-irradiated immature dendritic cells. J. Immunol. Res., 2016, 2419621. doi: 10.1155/2016/2419621.


Review

For citations:


Savchenko A.A., Borisov A.G., Kudryavtsev I.V., Gvozdev I.I., Moshev A.V. PHENOTYPIC PECULIARITIES OF DENDRITIС CELLS DIFFERENTIATED FROM BLOOD MONOCYTES IN PATIENTS WITH KIDNEY CANCER. Medical Immunology (Russia). 2018;20(2):215-226. (In Russ.) https://doi.org/10.15789/1563-0625-2018-2-215-226

Views: 1192


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 1563-0625 (Print)
ISSN 2313-741X (Online)