Nanomedicine Research Journal

Nanomedicine Research Journal

Renal cell carcinoma derived exosome as natural nanoparticles inhibits T cell proliferation and induces their apoptosis

Document Type : Original Research Article

Authors
Davood Babakhani 1
Danyal Daneshdoust 2
Amirhossein Baharvand 3
Azam Mivefroshan 4
Iman Raeisi 5
Bashar Zuhair Talib Al-Naqeeb 6
Farnaz Tavakoli 7
1 Assistant Professor of Hematology and Oncology, Hematology, Oncology Research Center and Stem Cell Transplantation (HORCST), Dr. Shariati hospital, Tehran University of Medical Sciences, Tehran Iran
2 Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran
3 Student Research Committee, Arak University of Medical Sciences, Arak, Iran
4 Nephrology and renal transplant research center ,urmia university of medical science,urmia , Iran
5 Iman.reeisy@gmail.com
6 Anesthesia technology department, Al-Turath University College , Al Mansour, Baghdad, Iraq
7 Assistant Professor of Nephrology, Tehran University of Medical Sciences, Shariati hospital, Nephrology ward, Tehran, Iran
10.22034/nmrj.2023.03.006
Abstract
Objective(s): To evaluate the anti-tumor effect of the renal cell carcinoma ACHN cell-exosome on human T cell biological parameters.
Methods: Human T cell was isolated from healthy donors. ACHN-cell derived exosome was procured and expression of the CD9 and CD63 was assessed using western blotting. The effects of the ACHN- exosome on T cell proliferation was measured using MTT assay within 24, 48, 72 and 96 hours of treatment with 500-2000 ng/ml exosome. Also, the apoptotic cell percentages in treated cells were assessed by Annexin/PI staining and flowcytometry upon exposure with 500 and 2000 ng/ml exosome within 96 hours of treatment.
Results: According to results, exosome therapy inhibited T cell proliferation more evidently at higher concentration.  Also, treatment with exosome caused an improvement in the apoptosis of the T cell within 96 hours of treatment.
Conclusions: Concerning the results, ACHN- exosome has negative effect on T cell viability and proliferation, facilitating immune evasion.
Keywords
T cell
Exosome
Renal cell carcinoma
Proliferation
Subjects
  1. Hsieh JJ, Purdue MP, Signoretti S, Swanton C, Albiges L, Schmidinger M, et al. Renal cell carcinoma. Nature reviews Disease primers, 2017;3(1):1-19. https://doi.org/10.1038/nrdp.2017.9
  2. Turco F, Tucci M, Di Stefano RF, Samuelly A, Bungaro M, Audisio M, et al. Renal cell carcinoma (RCC): fatter is better? A review on the role of obesity in RCC. Endocrine-related cancer, 2021;28(7):R207-R16. https://doi.org/10.1530/ERC-20-0457  
  3. Fottner A, Szalantzy M, Wirthmann L, Stähler M, Baur-Melnyk A, Jansson V, et al. Bone metastases from renal cell carcinoma: patient survival after surgical treatment. BMC musculoskeletal disorders, 2010;11(1):1-6. https://doi.org/10.1186/1471-2474-11-145  
  4. Jackson RJ, Gokaslan ZL, Arvinloh S-C. Metastatic renal cell carcinoma of the spine: surgical treatment and results. Journal of Neurosurgery: Spine, 2001;94(1):18-24. https://doi.org/10.3171/spi.2001.94.1.0018  
  5. Fogli S, Porta C, Del Re M, Crucitta S, Gianfilippo G, Danesi R, et al. Optimizing treatment of renal cell carcinoma with VEGFR-TKIs: a comparison of clinical pharmacology and drug-drug interactions of anti-angiogenic drugs. Cancer Treatment Reviews, 2020;84:101966. https://doi.org/10.1016/j.ctrv.2020.101966  
  6. Brighi N, Farolfi A, Conteduca V, Gurioli G, Gargiulo S, Gallà V, et al. The interplay between inflammation, anti-angiogenic agents, and immune checkpoint inhibitors: Perspectives for renal cell cancer treatment. Cancers, 2019;11(12):1935. https://doi.org/10.3390/cancers11121935  
  7. Virumbrales-Muñoz M, Ayuso JM, Loken JR, Denecke KM, Rehman S, Skala MC, et al. Microphysiological model of renal cell carcinoma to inform anti-angiogenic therapy. Biomaterials, 2022;283:121454. https://doi.org/10.1016/j.biomaterials.2022.121454  
  8. Jeppesen DK, Fenix AM, Franklin JL, Higginbotham JN, Zhang Q, Zimmerman LJ, et al. Reassessment of exosome composition. Cell, 2019;177(2):428-45. e18. https://doi.org/10.1016/j.cell.2019.02.029  
  9. Yazdanpanah S, Esmaeili S, Bashash D, Nayeri ND, Farahani ME, Gharehbaghian A. Cytotoxic and apoptogenic activity of Bryonia aspera extract on pre-B acute lymphoblastic leukemia cell lines. International Journal of Hematology-Oncology and Stem Cell Research, 2018;12(3):204.  
  10. Esfini-Farahani M, Farshdousti-Hagh M, Bashash D, Esmaeili S, Dehghan-Nayeri N, Yazdanpanah S, et al. Analysis of cytotoxic activity and synergistic effect of curcuma longa extract in combination with prednisolone on acute lymphoblastic leukemia cell lines. International Journal of Cancer Management, 2017;10(11). https://doi.org/10.5812/ijcm.14174  
  11. Wang L, Yang G, Zhao D, Wang J, Bai Y, Peng Q, et al. CD103-positive CSC exosome promotes EMT of clear cell renal cell carcinoma: role of remote MiR-19b-3p. Molecular cancer, 2019;18(1):1-15. https://doi.org/10.1186/s12943-019-0997-z  
  12. Song S, Long M, Yu G, Cheng Y, Yang Q, Liu J, et al. Urinary exosome miR‐30c‐5p as a biomarker of clear cell renal cell carcinoma that inhibits progression by targeting HSPA5. Journal of cellular and molecular medicine, 2019;23(10):6755-65. https://doi.org/10.1111/jcmm.14553  
  13. Zadi Heydarabad M, Baharaghdam S, Azimi A, Mohammadi H, Eivazi Ziaei J, Yazdanpanah B, et al. The role of tumor suppressor of resveratrol and prednisolone by downregulation of YKL‐40 expression in CCRF‐CEM cell line. Journal of cellular biochemistry, 2019;120(3):3773-9. https://doi.org/10.1002/jcb.27659  
  14. Zhang W, Zheng X, Yu Y, Zheng L, Lan J, Wu Y, et al. Renal cell carcinoma-derived exosomes deliver lncARSR to induce macrophage polarization and promote tumor progression via STAT3 pathway. International journal of biological sciences, 2022;18(8):3209-22. https://doi.org/10.7150/ijbs.70289  
  15. Wang X, Shi Q, Cui L, Wang K, Gong P, He X, et al. Tumor-derived exosomes facilitate tumor cells escape from drug therapy in clear cell renal cell carcinoma. Translational Cancer Research, 2020;9(5):3416. https://doi.org/10.21037/tcr-19-2246  
  16. Zhao L, Liu W, Xiao J, Cao B. The role of exosomes and "exosomal shuttle microRNA" in tumorigenesis and drug resistance. Cancer letters, 2015;356(2):339-46. https://doi.org/10.1016/j.canlet.2014.10.027  
  17. Karami Fath M, Azargoonjahromi A, Jafari N, Mehdi M, Alavi F, Daraei M, et al. Exosome application in tumorigenesis: diagnosis and treatment of melanoma. Medical Oncology, 2022;39(2):19. https://doi.org/10.1007/s12032-021-01621-8  
  18. Raimondo S, Pucci M, Alessandro R, Fontana S. Extracellular vesicles and tumor-immune escape: Biological functions and clinical perspectives. International journal of molecular sciences, 2020;21(7):2286. https://doi.org/10.3390/ijms21072286  
  19. Wieckowski EU, Visus C, Szajnik M, Szczepanski MJ, Storkus WJ, Whiteside TL. Tumor-derived microvesicles promote regulatory T cell expansion and induce apoptosis in tumor-reactive activated CD8+ T lymphocytes. The Journal of Immunology, 2009;183(6):3720-30. https://doi.org/10.4049/jimmunol.0900970  
  20. Wieckowski E, Whiteside TL. Human tumor-derived vs dendritic cell-derived exosomes have distinct biologic roles and molecular profiles. Immunologic research, 2006;36:247-54. https://doi.org/10.1385/IR:36:1:247  
  21. Garrido F, Aptsiauri N. Cancer immune escape: MHC expression in primary tumours versus metastases. Immunology, 2019;158(4):255-66. https://doi.org/10.1111/imm.13114  
  22. Maybruck BT, Pfannenstiel LW, Diaz-Montero M, Gastman BR. Tumor-derived exosomes induce CD8+ T cell suppressors. Journal for immunotherapy of cancer, 2017;5:1-15. https://doi.org/10.1186/s40425-017-0269-7  
  23. Siegel RM, Ka-Ming Chan F, Chun HJ, Lenardo MJ. The multifaceted role of Fas signaling in immune cell homeostasis and autoimmunity. Nature immunology, 2000;1(6):469-74. https://doi.org/10.1038/82712  
  24. Kim JW, Wieckowski E, Taylor DD, Reichert TE, Watkins S, Whiteside TL. Fas ligand-positive membranous vesicles isolated from sera of patients with oral cancer induce apoptosis of activated T lymphocytes. Clinical Cancer Research, 2005;11(3):1010-20. https://doi.org/10.1158/1078-0432.1010.11.3
Nanomedicine Research Journal
Volume 8, Issue 3
Summer 2023
Pages 277-282