Magnetically sensitive nanocomplex enhances antitumor efficacy of dendritic cell-based immunotherapy
DOI:
https://doi.org/10.32471/exp-oncology.2312-8852.vol-43-no-3.16507Keywords:
antitumor effect, dendritic cells, iron oxide nanoparticles, magnetic field, mouse sarcomaAbstract
Summary. Background: One of the major factors restricting in vivo efficacy of dendritic cells (DCs) based immunotherapy is the inefficient migration of these cells to the lymphoid tissue, wherein DCs activate antigen-specific T cells. A fundamentally new approach for the possibility of enhancing the antitumor effects of DC-based immunotherapy may be the use of magnetically sensitive nanocomplexes to increase the target delivery of DCs to the lymph nodes of the recipient. Aim: To study the antitumor and immunomodulatory effects of the DC-nanovaccine with magnetosensitive properties and its influence on the immunosuppressive tumor microenvironment in mice with sarcoma 37. Materials and Methods: The antitumor, antimetastatic and immunomodulatory effects of DCs loaded with magnetic nanocomplex under magnetic field (MF) control in mice with sarcoma 37 have been investigated. Results: Combined therapy contributed to a significant reduction in tumor volume and weight compared to the control group of mice and mice that received the DC vaccine without MF. Therapy with magnetically sensitive DC nanovaccine with and without the addition of the MF was accompanied by a significant down-regulation of the level of FoxP3, transforming growth factor β, interleukin (IL)-10 and vascular endothelial growth factors, mRNA expression in tumor tissues. A significant increase in interferon-γ and IL-4 mRNA expression was found in mice treated with the magnetically sensitive DC nanovaccine under MF control. Conclusion: A significant increase in the antitumor efficacy of the DC vaccine can be achieved using magnetosensitive nanocarriers of tumor antigens under MF control.
References
Baldin AV, Savvateeva LV, Bazhin AV, et al. Dendritic cells in anticancer vaccination: rationale for ex vivo loading or in vivo targeting. Cancers (Basel) 2020; 12: 590–632. https://doi.org/10.3390/cancers12030590.
Gu Y, Zhao X, Song X. Ex vivo pulsed dendritic cell vaccination against cancer. Acta Pharmacologica Sinica 2020; 41: 959–69. https://doi.org/10.1038/s41401-020-0415-5.
Cancel J-C, Crozat K, Dalod M, Mattiuz R. Are conventional type 1 dendritic cells critical for protective antitumor immunity and how? Front Immunol 2019; 10: 9. https://doi.org/10.3389/fimmu.2019.00009.
Jin H, Qian Y, Dai Y, et al. Magnetic enrichment of dendritic cell vaccine in lymph node with fluorescent-magnetic nanoparticles enhanced cancer immunotherapy. Theranostics 2016; 6: 2000–14. https://doi.org/10.7150/thno.15102.
Long CM, van Laarhoven HWM, Bulte JWM, et al. Magnetovaccination as a novel method to assess and quantify dendritic cell tumor antigen capture and delivery to lymph nodes. Cancer Res 2009; 69: 3180–7. https://doi.org/10.1158/0008-5472.CAN-08-3691.
Stagg AJ, Burke F, Hill S, Knight SC. Isolation of mouse spleen dendritic cells. Methods Mol Med 2001; 64: 9–22. https://doi.org/10.1385/1-59259-150-7:9.
Mou Y, Chen B, Zhang Yu, et al. Influence of synthetic superparamagnetic iron oxide on dendritic cells. Int J Nanomedicine 2011; 6: 1779–86. https://doi.org/10.2147/IJN.S23240.
Khranovskaya N, Orel V, Grinevich Yu, et al. Mechanical heterogenization of Lewis lung carcinoma cells can improve antimetastatic effect of dendritic cells. J Mechanics Med Biol 2012; 12. doi: https://doi.org/10.1142/S0219519411004757.
Kim R, Emi M, Tanabe K, Arihiro K. Tumor-driven evolution of immunosuppressive networks during malignant progression. Cancer Res 2006; 66: 5527–36. https://doi.org/10.1158/0008-5472.CAN-05-4128.
Ohkura N, Hamaguchi M, Morikawa H, et al. T cell receptor stimulation-induced epigenetic changes and Foxp3 expression are independent and complementary events required for Treg cell development. Immunity 2012; 37: 785–99. https://doi.org/10.1016/j.immuni.2012.09.010.
Li C, Jiang P, Wei S, et al. Regulatory T cells in tumor microenvironment: new mechanisms, potential therapeutic strategies and future prospects. Mol Cancer 2020; 19: 116–38. HTTPS://DOI.ORG/10.1186/s12943-020-01234-1.
Ugur M, Mueller SN. T cell and dendritic cell interactions in lymphoid organs: More than just being in the right place at the right time. Immunol Rev 2019; 289: 115–28. https://doi.org/10.1111/imr.12753.
Seyfizadeh N, Muthuswamy R, Mitchell DA, et al. Migration of dendritic cells to the lymph nodes and its enhancement to drive anti-tumor responses. Crit Rev Oncol Hematol 2016; 107: 100–10. https://doi.org/10.1016/j.critrevonc.2016.09.002.
Sabado RL, Bhardwaj N. Directing dendritic cell immunotherapy towards successful cancer treatment. Immunotherapy 2010; 2: 37–56. https://doi.org/10.2217/imt.09.43.
Khranovska NM. [The role of dendritic cells in activation of antitumor immununity (experimental and clinical-immunological study)]. Abstr Doctoral Diss. Kyiv, 2017, 52 p (in Ukrainian).
Kim CG, Kye Y-C, Yun C-H. The Role of Nanovaccine in cross-presentation of antigen-presenting cells for the activation of CD8+ T cell responses. Pharmaceutics 2019; 11: 612–33. https://doi.org/10.3390/pharmaceutics11110612.
Warrier VU, Makandar AI, Garg M, et al. Engineering anti-cancer nanovaccine based on antigen cross-presentation. Biosci Rep 2019; 39: BSR20193220. https://doi.org/10.1042/BSR20193220.
Shen H. Enhanced and prolonged cross-presentation following endosomal escape of exogenous antigens encapsulated in biodegradable nanoparticles. Immunology 2006; 117: 78–88. https://doi.org/10.1111/j.1365-2567.2005.02268.x.
Smith DM, Simon JK, Baker Jr JR. Applications of nanotechnology for immunology. Nat Rev Immunol 2013; 13: 592–606. https://doi.org/10.1038/nri3488.
Mahjub R, Jatana S, Lee SE, et al. Recent advances in applying nanotechnologies for cancer immunotherapy. J Control Release 2018; 288: 239–63. https://doi.org/10.1016/j.jconrel.2018.09.010.
Chittasupho C, Shannon L, Siahaan TJ, et al. Nanoparticles targeting dendritic cell surface molecules effectively block T cell conjugation and shift response. ACS Nano 2011; 5: 1693–1702. https://doi.org/10.1021/nn102159g.
Israelsson P, Labani-Motlagh A, Nagaev I, et al. Assessment of cytokine mRNA expression profiles in tumor microenvironment and peripheral blood mononuclear cells of patients with high-grade serous carcinoma of the ovary. J Cancer Sci Ther 2017; 9: 422–9. https://doi.org/10.4172/1948-5956.1000453.
McDonnell AM, Currie AJ, Brown M, et al. Tumor cells, rather than dendritic cells, deliver antigen to the lymph node for cross-presentation. Oncoimmunology 2012; 1: 840–6. https://doi.org/10.4161/onci.20493.
Hinshaw DC, Shevde LA. The tumor microenvironment innately modulates cancer progression. Cancer Res 2019; 79: 4557–66. https://doi.org/10.1158/0008-5472.CAN-18-3962.
Peng X, He Y, Huang J, et al. Metabolism of dendritic cells in tumor microenvironment: for immunotherapy. Front Immunol 2021; 12: 613492. https://doi.org/10.3389/fimmu.2021.613492.
Blasio SD, van Wigcheren GF, Becker A, et al. The tumour microenvironment shapes dendritic cell plasticity in a human organotypic melanoma culture. Nat Commun 2020; 11: 2749–65. https://doi.org/10.1038/s41467-020-16583-0.
Pitt JM, Marabelle A, Eggermont A, et al. Targeting the tumor microenvironment: removing obstruction to anticancer immune responses and immunotherapy. Ann Oncol 2016; 27: 1482–92. https://doi.org/10.1093/annonc/mdw168.
Liu Y, Guo J, Huang L. Modulation of tumor microenvironment for immunotherapy: focus on nanomaterial-based strategies. Theranostics 2020; 10: 3099–117. https://doi.org/10.7150/thno.42998.
Gardner A, Ruffell B. Dendritic cells and cancer immunity. Trends Immunol 2016; 37: 855–65. https://doi.org/10.1016/j.it.2016.09.006.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2023 Experimental Oncology
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
