ДЕНДРИТНЫЕ КЛЕТКИ В ТЕРАПИИ АДЕНОКАРЦИНОМЫ МОЛОЧНОЙ ЖЕЛЕЗЫ

DOI: https://doi.org/10.29296/24999490-2019-04-02

А.А. Чернышева(1), И.В. Чехонин(2), О.И. Гурина(2), профессор, И.И. Шепелева(2, 3), кандидат биологических наук, доцент, Т.Н. Попова(1), доктор биологических наук, профессор 1-ФГБОУ ВО «Воронежский государственный университет», Российская Федерация, 394018, Воронеж, Университетская площадь, 1; 2-ФГБУ «Национальный медицинский исследовательский центр психиатрии и наркологии им. В.П. Сербского» Минздрава Российской Федерации, Российская Федерация, 119034, Москва, Кропоткинский пер., д. 23; 3-ФГБОУ ВО «Российский национальный исследовательский медицинский университет им. Н.И. Пирогова» Минздрава России, Российская Федерация, 117997, Москва, ул. Островитянова, д. 1 E-mail: 79202208606@yandex.ru

Будучи профессиональными антигенпрезентирующими клетками, обладающими функциональной пластичностью, дендритные клетки (ДК) широко изучаются в доклинических и клинических исследованиях вакцин против различных видов злокачественных опухолей. В отношении некоторых из них была доказана эффективность. Тем не менее в мире еще не существует ни одной официально одобренной дендритноклеточной вакцины (ДКВ) для лечения аденокарциномы молочной железы (АМЖ). Знание и понимание основных функций ДК, а также разработка способов усиления эффекта подобных вакцин могут способствовать развитию этого направления. В представленном обзоре рассматриваются основные типы ДК с акцентом на их роль в патогенезе опухоли молочной железы, а также рассматриваются основные механизмы захвата, процессинга и презентации антигенов. Кроме того, значительное внимание уделяется существующим исследованиям, касающимся терапии АМЖ ДКВ, применяющимися как в качестве монотерапии, так и в комбинации с другими терапевтическими стратегиями.
Ключевые слова: 
дендритные клетки, иммунотерапия

Список литературы: 
  1. Каприн А.Д., Старинский В.В., Петрова Г.В. Злокачественные новообразования в России в 2017 г. (заболеваемость и смертность). М.: МНИОИ им. П.А. Герцена – филиал ФГБУ «НМИЦ радиологии» Минздрава России, 2018; 250.
  2. [Kaprin A.D., Starinsky V.V., Petrova G.V. Malignant neoplasms in Russia (morbidity and mortality) in 2017. M., 2018; 250 (in Russian)]
  3. Bray F., Ferlay J., Soerjomataram I., Siegel R.L., Torre L.A., Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer J. for Clinicians. 2018; 68 (6): 394–424. https://doi.org/10.3322/caac.21492
  4. Министерство здравоохранения РФ. Клинические рекомендации: рак молочной железы (http://oncology-association.ru/docs/rak_molochnoy_zhelezy.pdf)
  5. [The Ministry of Health of the Russian Federation. Clinical guidelines: breast cancer (http://oncology-association.ru/docs/rak_molochnoy_zhelezy.pdf) (in Russian)]
  6. Ju J., Zhu A-J., Yuan P. Progress in targeted therapy for breast cancer. Chronic Diseases and Translational Medicine. 2018; 4 (3): 164–75. https://doi.org/10.1016/j.cdtm.2018.04.002
  7. Baklaushev V.P., Grinenko N.F., Yusubalieva G.M., Abakumov M.A., Gubskii I.L., Cherepanov S.A., Kashparov I.A., Burenkov M.S., Rabinovich E.Z., Ivanova N.V., Antonova O.M., Chekhonin V.P. Modeling and Integral X-Ray, Optical, and MRI Visualization of Multiorgan Metastases of Orthotopic 4T1 Breast Carcinoma in BALB/c Mice. Bulletin of Experimental Biology and Medicine. 2015; 158 (4): 581–8. https://doi.org/10.1007/s10517-015-2810-3
  8. Wu L., Galy A. The development of dendritic cells from hematopoietic precursors. In: Dendritic Cells (Second Edition): Biology and Clinical Applications. (M.T. Lotze, A.W. Thomson). Academic Press Co. 2001; 3–12.
  9. Roberts E.W., Broz M.L., Binnewies M., Headley M.B., Nelson A.E., Wolf D.M., Kaisho T., Bogunovic D., Bhardwaj N., Krummel M.F. Critical Role for CD103+/CD141+ Dendritic Cells Bearing CCR7 for Tumor Antigen Trafficking and Priming of T Cell Immunity in Melanoma. Cancer Cell. 2016; 30 (2): 324–36. https://doi.org/10.1016/j.ccell.2016.06.003
  10. Krishnaswamy J.K., Gowthaman U., Zhang B., Mattsson J., Szeponik L., Liu D., Wu R., White T., Calabro S., Xu L., Collet M.A., Yurieva M., Alsén S., Fogelstrand P., Walter A., Heath W.R., Mueller S.N., Yrlid U., Williams A., Eisenbarth S.C. Migratory CD11b+ conventional dendritic cells induce T follicular helper cell-dependent antibody responses. Science Immunology. 2017; 2 (18): eaam9169. https://doi.org/10.1126/sciimmunol.aam9169
  11. Yang G-X., Lian Z-X., Kikuchi K., Moritoki Y., Ansari A.A., Liu Y-J., Ikehara S., Gershwin M.E. Plasmacytoid Dendritic Cells of Different Origins Have Distinct Characteristics and Function: Studies of Lymphoid Progenitors versus Myeloid Progenitors. J. Immunol. 2005; 175 (11): 7281–7. https://doi.org/10.4049/jimmunol.175.11.7281
  12. Zhang H., Gregorio J.D., Iwahori T., Zhang X., Choi O., Tolentino L.L., Prestwood T., Carmi Y., Engleman E.G. A distinct subset of plasmacytoid dendritic cells induces activation and differentiation of B and T lymphocytes. Proc. Natl. Acad. Sci USA. 2017; 114 (8): 1988–93. https://doi.org/10.1073/pnas.1610630114
  13. Sawant A., Ponnazhagan S. Role of plasmacytoid dendritic cells in breast cancer bone dissemination. Oncoimmunology, 2013; 2 (2): e22983. https://doi.org/10.4161/onci.22983
  14. Wu J., Li S., Yang Y., Zhu S., Zhang M., Qiao Y., Liu Y-J., Chen J. TLR-activated plasmacytoid dendritic cells inhibit breast cancer cell growth in vitro and in vivo. Oncotarget. 2017; 8: 11708–18. https://doi.org/10.18632/oncotarget.14315
  15. Polak M.E., Newell L., Taraban V.Y., Pickard C., Healy E., Friedmann P.S., Al-Shamkhani A., Ardern-Jones M.R. CD70–CD27 Interaction Augments CD8+ T-Cell Activation by Human Epidermal Langerhans Cells. J. Invest Dermatol. 2012; 132 (6): 1636–44. https://doi.org/10.1038/jid.2012.26
  16. Tsuge T., Yamakawa M., Tsukamoto M. Infiltrating dendritic/Langerhans cells in primary breast cancer. Breast Cancer Res Treat. 2000; 59 (2): 141–52. https://doi.org/10.1023/A:1006396216933
  17. Amorim K.N.S., Chagas D.C.G., Sulczewski F.B., Boscardin S.B. Dendritic Cells and Their Multiple Roles during Malaria Infection. J. of Immunology Research. 2016; 2016: 2926436. https://doi.org/10.1155/2016/2926436
  18. Liu Z., Roche P.A. Macropinocytosis in phagocytes: regulation of MHC class-II-restricted antigen presentation in dendritic cells. Front. Physiol. 2015; 6: 1. https://doi.org/10.3389/fphys.2015.00001
  19. Moreau H.D., Blanch-Mercader C., Attia R., Alraies Z., Maurin M., Bousso P., Joanny J-F., Voituriez R., Piel M., Lennon-Dumenil A-M. Macropinocytosis overcomes directional bias due to hydraulic resistance to enhance space exploration by dendritic cells. bioRxiv. 2018; 272682. https://doi.org/10.1101/272682
  20. Chapman H.A. Endosomal proteases in antigen presentation. Curr Opin Immunol. 2006; 18 (1): 78–84. https://doi.org/10.1016/j.coi.2005.11.011
  21. Schmidt M., Lill J.R. MHC class I presented antigens from malignancies: A perspective on analytical characterization & immunogenicity. J. of Proteomics. 2019; 191: 48–57. https://doi.org/10.1016/j.jprot.2018.04.021
  22. Basha G., Lizée G., Reinicke A.T., Seipp R.P., Omilusik K.D., Jefferies W.A. MHC Class I Endosomal and Lysosomal Trafficking Coincides with Exogenous Antigen Loading in Dendritic Cells. PLoS One. 2008; 3 (9): e3247. https://doi.org/10.1371/journal.pone.0003247
  23. Santambrogio L., Sato A.K., Carven G.J., Belyanskaya S.L., Strominger J.L., Stern L.J. Extracellular antigen processing and presentation by immature dendritic cells. Proc. Natl. Acad. Sci. USA. 1999; 96 (26): 15056–61. https://doi.org/10.1073/pnas.96.26.15056
  24. Талаев В.Ю., Плеханова М.В., Матвеичев А.В. Экспериментальные модели, пригодные для оценки влияния компонентов новых разрабатываемых вакцин на дифференцировку дендритных клеток. Медиаль. 2014; 2 (12): 135–53.
  25. [Talaev V.Ju., Plekhanova M.V., Matveichev A.V. In vitro models for investigation of vaccine component action upon dendritc cell maturation. Medial. 2014; 2 (12): 135–53 (in Russian)]
  26. Constantino J., Gomes C., Falcão A., Cruz M.T., Neves B.M. Antitumor dendritic cell–based vaccines: lessons from 20 years of clinical trials and future perspectives. Transl Res. 2016; 168: 74–95. https://doi.org/10.1016/j.trsl.2015.07.008
  27. Maj T., Slawek A., Chelmonska-Soyta A. CD80 and CD86 Costimulatory Molecules Differentially Regulate OT-II CD4+ T Lymphocyte Proliferation and Cytokine Response in Cocultures with Antigen-Presenting Cells Derived from Pregnant and Pseudopregnant Mice. Mediators Inflamm. 2014; 2014: 769239. https://doi.org/10.1155/2014/769239
  28. Gong J., Avigan D., Chen D., Wu Z., Koido S., Kashiwaba M., Kufe D. Activation of antitumor cytotoxic T lymphocytes by fusions of human dendritic cells and breast carcinoma cells. Proc. Natl. Acad. Sci. USA. 2000; 97 (6): 2715–8. https://doi.org/10.1073/pnas.050587197
  29. Neidhardt-Berard E-M., Berard F., Banchereau J., Palucka A.K. Dendritic cells loaded with killed breast cancer cells induce differentiation of tumor-specific cytotoxic T lymphocytes. Breast Cancer Res. 2004; 6: R322. https://doi.org/10.1186/bcr794
  30. Gervais A., Levêque J., Bouet-Toussaint F., Burtin F., Lesimple T., Sulpice L., Patard J.-J., Genetet N., Catros-Quemener V. Dendritic cells are defective in breast cancer patients: a potential role for polyamine in this immunodeficiency. Breast Cancer Res. 2005; 7 (3): 326–35. https://doi.org/10.1186/bcr1001
  31. Чехонин И.В., Гурина О.И., Черепанов С.А., Абакумов М.А., Ионова К.П., Жигарев Д.К., Макаров А.В., Чехонин В.П. Сенсибилизированные дендритные клетки для терапии экспериментальной глиомы. Бюллетень экспериментальной биологии и медицины. 2016; 161 (6): 747–52.
  32. [Chekhonin I.V., Gurina O.I., Cherepanov S.A., Abakumov M.A., Ionova K.P., Zhigarev D.K., Makarov A.V., Chekhonin V.P. Pulsed Dendritic Cells for the Therapy of Experimental Glioma. Byulleten Eksperimental’noi Biologii i Meditsiny. 2016; 161 (6): 747–52 (in Russian)]
  33. El Deeb N.M., Mehanna R.A. Assessment of maturation status of tumor-infiltrating dendritic cells in invasive ductal carcinoma of the breast: relation with vascular endothelial growth factor expression. Turk Patoloji Derg. 2013; 29 (3): 193–200. https://doi.org/10.5146/tjpath.2013.01186.
  34. Bohnenkamp H.R., Coleman J., Burchell J.M., Taylor-Papadimitriou J., Noll T. Breast carcinoma cell lysate-pulsed dendritic cells cross-prime MUC1-specific CD8+ T cells identified by peptide-MHC-class-I tetramers. Cell Immunol. 2004; 231 (1–2): 112–25. https://doi.org/10.1016/j.cellimm.2004.12.007
  35. Brossart P., Wirths S., Stuhler G., Reichardt V.L., Kanz L., Brugger W. Induction of cytotoxic T-lymphocyte responses in vivo after vaccinations with peptide-pulsed dendritic cells. Blood. 2000; 96: 3102–8.
  36. Lowenfeld L., Mick R., Datta J., Xu S., Fitzpatrick E., Fisher C.S., Fox K.R., DeMichele A., Zhang P.J., Weinstein S.P., Roses R.E., Czerniecki B.J. Dendritic Cell Vaccination Enhances Immune Responses and Induces Regression of HER2pos Ductal Carcinoma In Situ Independent of Route: Results of Randomized Selection Design Trial. Clin. Cancer Res. 2017; 23 (12): 2961–71. https://doi.org/10.1158/1078-0432.CCR-16-1924
  37. Cui H., Zhang W., Hu W., Liu K., Wang T., Ma N., Liu X., Liu Y., Jiang Y. Recombinant Mammaglobin A Adenovirus-Infected Dendritic Cells Induce Mammaglobin A-Specific CD8+ Cytotoxic T Lymphocytes against Breast Cancer Cells In Vitro. PLoS One. 2013; 8 (5): e63055. https://doi.org/10.1371/journal.pone.0063055
  38. Delirezh N., Moazzeni S.M., Shokri F., Shokrgozar M.A., Atri M., Kokhaei P. Autologous dendritic cells loaded with apoptotic tumor cells induce T cell-mediated immune responses against breast cancer in vitro. Cell. Immunol. 2009; 257 (1–2): 23–31. https://doi.org/10.1016/j.cellimm.2009.02.002
  39. Zheng J., Liu Q., Yang J., Ren Q., Cao W., Yang J., Yu Z., Yu F., Wu Y., Shi H., Liu W. Co-culture of apoptotic breast cancer cells with immature dendritic cells: a novel approach for DC based vaccination in breast cancer. Brazilian Journal of Medical and Biological Research. 2012; 45 (6): 510–5. https://doi.org/10.1590/S0100-879X2012007500061
  40. Avigan D., Vasir B., Gong J., Borges V., Wu Z., Uhl L., Atkins M., Mier J., McDermott D., Smith T., Giallambardo N., Stone C., Schadt K., Dolgoff J., Tetreault J.C., Villarroel M., Kufe D. Fusion Cell Vaccination of Patients with Metastatic Breast and Renal Cancer Induces Immunological and Clinical Responses. Clin. Cancer Res. 2004; 10 (14): 4699–708. https://doi.org/10.1158/1078-0432.CCR-04-0347
  41. Zhang P., Yi S., Li X., Liu R., Jiang H., Huang Z., Liu Y., Wu J., Huang Y. Preparation of Triple-Negative Breast Cancer Vaccine through Electrofusion with Day-3 Dendritic Cells. PLoS One. 2014; 9 (7): e102197. https://doi.org/10.1371/journal.pone.0102197
  42. Das M., Law S. Role of Tumor Microenvironment in Cancer Stem Cell Chemoresistance and recurrence. Int J. Biochem Cell Biol. 2018; 103 (2018): 115–24. https://doi.org/10.1016/j.biocel.2018.08.011
  43. Dashti A., Ebrahimi M., Hadjati J., Memarnejadian A., Moazzeni S.M. Dendritic cell based immunotherapy using tumor stem cells mediates potent antitumor immune responses. Cancer Lett. 2016; 374 (1): 175–85. https://doi.org/10.1016/j.canlet.2016.01.021
  44. Nguyen S.T., Nguyen H.L., Pham V.Q., Nguyen G.T., Tran C.D-T., Phan N.K., Pham P.V. Targeting specificity of dendritic cells on breast cancer stem cells: in vitro and in vivo evaluations. Onco Targets Ther. 2015; 8: 323–34. https://doi.org/10.2147/OTT.S77554
  45. Pham P.V., Le H.T., Vu B.T., Pham V.Q., Le P.M., Phan N.L., Trinh N.V., Nguyen H.T., Nguyen S.T., Nguyen T.L., Phan N.K. Targeting breast cancer stem cells by dendritic cell vaccination in humanized mice with breast tumor: preliminary results. Onco Targets Ther. 2016; 2016 (9): 4441–51. https://doi.org/10.2147/OTT.S105239
  46. Bryson P.D., Han X., Truong N., Wang P. Breast cancer vaccines delivered by dendritic cell targeted lentivectors induce potent antitumor immune responses and protect mice from mammary tumor growth. Vaccine. 2017; 35 (43): 5842–9. https://doi.org/10.1016/j.vaccine.2017.09.017
  47. Tang M., Liu Y., Zhang Q-C., Zhang P., Wu J-K., Wang J-N., Ruan Y., Huang Y. Antitumor efficacy of the Runx2‑dendritic cell vaccine in triple‑negative breast cancer in vitro. Oncology Lett. 2018; 16 (3): 2813–22. https://doi.org/10.3892/ol.2018.9001
  48. Rathinaraj P., Al-Jumaily A., Huh D.S. Internalization: acute apoptosis of breast cancer cells using herceptin-immobilized gold nanoparticles. Breast Cancer: Targets and Therapy. 2015; 2015 (7): 51–8. https://doi.org/10.2147/BCTT.S69834
  49. Acharya S., Fahima D., Sahoo S.K. Targeted epidermal growth factor receptor nanoparticle bioconjugates for breast cancer therapy. Biomaterials. 2009; 30 (29): 5737–50. https://doi.org/10.1016/j.biomaterials.2009.07.008
  50. Iranpour S., Nejati V., Delirezh N., Biparva P., Shirian S. Enhanced stimulation of anti-breast cancer T cells responses by dendritic cells loaded with poly lactic-co-glycolic acid (PLGA) nanoparticle encapsulated tumor antigens. J. Exp. Clin. Cancer Res. 2016; 35: 168. https://doi.org/10.1186/s13046-016-0444-6
  51. Kim S., Park S., Cho M.S., Lim W., Moon B-I., Sung S.H. Strong Correlation of Indoleamine 2,3-Dioxygenase 1 Expression with Basal-Like Phenotype and Increased Lymphocytic Infiltration in Triple-Negative Breast Cancer. J. of Cancer. 2017; 8 (1): 124–30. https://doi.org/10.7150/jca.17437
  52. Smith C., Chang M-Y., Parker K., Beury D., DuHadaway J.B., Flick H.E., Boulden J., Sutanto-Ward E., Soler A.P., Laury-Kleintop L.D., Mandik-Nayak L., Metz R., Ostrand-Rosenberg S., Prendergast G.C., Muller A.J. IDO Is a Nodal Pathogenic Driver of Lung Cancer and Metastasis Development. Cancer Discov. 2012; 2 (8): 722–35. https://doi.org/10.1158/2159-8290.CD-12-0014
  53. Soliman H., Khambati F., Han H.S., Ismail-Khan R., Bui M.M., Sullivan D.M., Antonia S. A phase-1/2 study of adenovirus-p53 transduced dendritic cell vaccine in combination with indoximod in metastatic solid tumors and invasive breast cancer. Oncotarget. 2018; 9 (11): 10110–7. https://doi.org/10.18632/oncotarget.24118
  54. Jadidi-Niaragh F., Atyabi F., Rastegari A., Kheshtchin N., Arab S., Hassannia H., Ajami M., Mirsanei Z., Habibi S., Masoumi F., Noorbakhsh F., Shokri F., Hadjati J. CD73 specific siRNA loaded chitosan lactate nanoparticles potentiate the antitumor effect of a dendritic cell vaccine in 4T1 breast cancer bearing mice. J. Control Release. 2017; 246 (2017): 46–59. https://doi.org/10.1016/j.jconrel.2016.12.012
  55. Gall V.A., Philips A.V., Qiao N., Clise-Dwyer K., Perakis A.A., Zhang M., Clifton G.T., Sukhumalchandra P., Ma Q., Reddy S.M., Yu D., Molldrem J.J., Peoples G.E., Alatrash G., Mittendorf E.A. Trastuzumab Increases HER2 Uptake and Cross-Presentation by Dendritic Cells. Cancer Res. 2017; 77 (19): 5374–83. https://doi.org/10.1158/0008-5472.CAN-16-2774