A.A. Chernysheva(1), I.V. Chekhonin(2), O.I. Gurina(2), I.I. Shepeleva(2, 3), T.N. Popova(1) 1-Voronezh State University, Universitetskaya pl., 1, Voronezh, 394018, Russian Federation; 2-V.P. Serbsky National Medical Research Centre for Psychiatry and Narcology, Kropotkinskiy bystreet, 23, Moscow, 119034, Russian Federation; 3-N.I. Pirogov Russian National Research Medical University, Ostrovitianova str., 1, Moscow, 117997, Russian Federation E-mail:

Dendritic cells (DC), as professional antigen-presenting cells with functional plasticity, are widely studied in preclinical and clinical research of vaccines against various types of malignant tumors. Some of the studies DС have proved their efficiency. However, all over the world, there is no officially approved DC vaccine for the treatment of breast cancer. Knowledge and understanding of fundamental functions of DC, as well as the development of methods enhancing the effect of such vaccines, may contribute to the progress in this direction. In this review, we consider the features of the main types of DC and their role in the pathogenesis of breast cancer. Also, we describe the mechanisms of antigen uptake, processing, and presentation. In addition, considerable attention is paid to the current research of DC-based treatment of breast adenocarcinoma as DC are studied both as monotherapy or in combination with other therapeutic strategies.
breast cancer, dendritic cells, immunotherapy

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.
  4. Министерство здравоохранения РФ. Клинические рекомендации: рак молочной железы (
  5. [The Ministry of Health of the Russian Federation. Clinical guidelines: breast cancer ( (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.
  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.
  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.
  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.
  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.
  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.
  13. Sawant A., Ponnazhagan S. Role of plasmacytoid dendritic cells in breast cancer bone dissemination. Oncoimmunology, 2013; 2 (2): e22983.
  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.
  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.
  16. Tsuge T., Yamakawa M., Tsukamoto M. Infiltrating dendritic/Langerhans cells in primary breast cancer. Breast Cancer Res Treat. 2000; 59 (2): 141–52.
  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.
  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.
  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.
  20. Chapman H.A. Endosomal proteases in antigen presentation. Curr Opin Immunol. 2006; 18 (1): 78–84.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.