Exosomes Derived from Heat‐shocked Tumor Cells Promote In vitro Maturation of Bone Marrow-derived Dendritic Cells
-
Neda Heidari
,
Hajar Abbasi-kenarsari
,
Bahare Niknam
,
Ali Asadirad
,
Davar Amani
,
Zahra Mirsanei
,
Seyed Mahmood Hashemi
Abstract
Dendritic cells (DCs), professional antigen-presenting cells that process and deliver antigens using MHC II/I molecules, can be enhanced in numerous ways. Exosomes derived from heat‐shocked tumor cells (HS‐TEXs) contain high amounts of heat-shock proteins (HSPs). HSPs, as chaperons, can induce DC maturation. This study aimed to investigate whether HS‐TEXs can promote DC maturation.
To generate DC, bone marrow-derived cells were treated with Interleukin-4 and GM-CSF. Exosomes were isolated from heat-treated CT-26 cells. The expression level of HSP in exosomes was checked by western blot and the increase in the expression of this protein was observed. Then, HS‐TEXs were co-cultured with iDCs to determine DC maturity, and then DCs were co-cultured with lymphocytes to determine DC activity.
Our results showed that DCs treated with HS‐TEXs express high levels of molecules involved in DC maturation and function including MHCII, CD40, CD83, and CD86. HS‐TEXs caused phenotypic and functional maturation of DCs. In addition, flow cytometric results reflected a higher proliferative response of lymphocytes in the iDC / Tex + HSP group.
HS‐TEXs could be used as a strategy to improve DC maturation and activation.
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19. He SB, Sun K, Wang L, Li DC, Zhang YY. [GM-CSF gene-modified dendritic cell vaccine enhances antitumor immunity in vitro]. Zhonghua Zhong Liu Za Zhi. 2010;32(6):410-4.
20. Wang HY, Fu JC, Lee YC, Lu PJ. Hyperthermia stress activates heat shock protein expression via propyl isomerase 1 regulation with heat shock factor 1. Mol Cell Biol. 2013;33(24):4889-99.
21. McNulty S, Colaco CA, Blandford LE, Bailey CR, Baschieri S, Todryk S. Heat-shock proteins as dendritic cell-targeting vaccines--getting warmer. Immunology. 2013;139(4):407-15.
22. Wronska AK, Bogus MI. Heat shock proteins (HSP 90, 70, 60, and 27) in Galleria mellonella (Lepidoptera) hemolymph are affected by infection with Conidiobolus coronatus (Entomophthorales). PLoS One. 2020;15(2):e0228556.
23. Zhu H, Fang X, Zhang D, Wu W, Shao M, Wang L, Gu J. Membrane-bound heat shock proteins facilitate the uptake of dying cells and cross-presentation of cellular antigen. Apoptosis. 2016;21(1):96-109.
24. Cho JA, Lee YS, Kim SH, Ko JK, Kim CW. MHC independent anti-tumor immune responses induced by Hsp70-enriched exosomes generate tumor regression in murine models. Cancer Lett. 2009;275(2):256-65.
25. Mirsanei Z, Habibi S, Kheshtchin N, Mirzaei R, Arab S, Zand B, et al. Optimized dose of dendritic cell-based vaccination in experimental model of tumor using artificial neural network. 2020:172-82.
26. Thery C, Zitvogel L, Amigorena S. Exosomes: composition, biogenesis and function. Nat Rev Immunol. 2002;2(8):569-79.
27. Heidari N, Abbasi-Kenarsari H, Namaki S, Baghaei K, Zali MR, Ghaffari Khaligh S, Hashemi SM. Adipose-derived mesenchymal stem cell-secreted exosome alleviates dextran sulfate sodium-induced acute colitis by Treg cell induction and inflammatory cytokine reduction. J Cell Physiol. 2021.
28. Wolfers J, Lozier A, Raposo G, Regnault A, Thery C, Masurier C, et al. Tumor-derived exosomes are a source of shared tumor rejection antigens for CTL cross-priming. Nat Med. 2001;7(3):297-303.
29. Reddy VS, Madala SK, Trinath J, Reddy GB. Extracellular small heat shock proteins: exosomal biogenesis and function. Cell Stress Chaperones. 2018;23(3):441-54.
30. Todryk SM, Gough MJ, Pockley AG. Facets of heat shock protein 70 show immunotherapeutic potential. Immunology. 2003;110(1):1-9.
31. Multhoff G, Botzler C, Wiesnet M, Muller E, Meier T, Wilmanns W, Issels RD. A stress-inducible 72-kDa heat-shock protein (HSP72) is expressed on the surface of human tumor cells, but not on normal cells. Int J Cancer. 1995;61(2):272-9.
32. Naseri M, Bozorgmehr M, Zoller M, Ranaei Pirmardan E, Madjd Z. Tumor-derived exosomes: the next generation of promising cell-free vaccines in cancer immunotherapy. Oncoimmunology. 2020;9(1):1779991.
33. Hauet-Broere F, Wieten L, Guichelaar T, Berlo S, van der Zee R, Van Eden W. Heat shock proteins induce T cell regulation of chronic inflammation. Ann Rheum Dis. 2006;65 Suppl 3:iii65-8.
34. Ferrarini M, Heltai S, Zocchi MR, Rugarli C. Unusual expression and localization of heat-shock proteins in human tumor cells. Int J Cancer. 1992;51(4):613-9.
35. Hao S, Bai O, Li F, Yuan J, Laferte S, Xiang J. Mature dendritic cells pulsed with exosomes stimulate efficient cytotoxic T-lymphocyte responses and antitumour immunity. Immunology. 2007;120(1):90-102.
36. Hsu DH, Paz P, Villaflor G, Rivas A, Mehta-Damani A, Angevin E, et al. Exosomes as a tumor vaccine: enhancing potency through direct loading of antigenic peptides. J Immunother. 2003;26(5):440-50.
2. Rahbar S, Shafiekhani S, Allahverdi A, Jamali A, Kheshtchin N, Ajami M, et al. Agent-based modeling of tumor and immune system interactions in combinational therapy with low-dose 5-fluorouracil and dendritic cell vaccine in melanoma B16F10. Iranian Journal of Allergy, Asthma and Immunology. 2022;21(2):151-66.
3. Palucka K, Banchereau J. Cancer immunotherapy via dendritic cells. Nat Rev Cancer. 2012;12(4):265-77.
4. Krysko DV, Garg AD, Kaczmarek A, Krysko O, Agostinis P, Vandenabeele P. Immunogenic cell death and DAMPs in cancer therapy. Nat Rev Cancer. 2012;12(12):860-75.
5. Mirsanei Z, Habibi S, Kheshtchin N, Mirzaei R, Arab S, Zand B, et al. Optimized dose of dendritic cell-based vaccination in experimental model of tumor using artificial neural network. Iranian Journal of Allergy, Asthma and Immunology. 2020:172-82.
6. Mahmoodzadeh Hosseini H, Halabian R, Amin M, Imani Fooladi AA. Texosome-based drug delivery system for cancer therapy: from past to present. Cancer Biol Med. 2015;12(3):150-62.
7. Kunigelis KE, Graner MW. The Dichotomy of Tumor Exosomes (TEX) in Cancer Immunity: Is It All in the ConTEXt? Vaccines (Basel). 2015;3(4):1019-51.
8. Udono H, Srivastava PK. Heat shock protein 70-associated peptides elicit specific cancer immunity. J Exp Med. 1993;178(4):1391-6.
9. Sen K, Sheppe AEF, Singh I, Hui WW, Edelmann MJ, Rinaldi C. Exosomes released by breast cancer cells under mild hyperthermic stress possess immunogenic potential and modulate polarization in vitro in macrophages. Int J Hyperthermia. 2020;37(1):696-710.
10. Chen T, Guo J, Yang M, Zhu X, Cao X. Chemokine-containing exosomes are released from heat-stressed tumor cells via lipid raft-dependent pathway and act as efficient tumor vaccine. J Immunol. 2011;186(4):2219-28.
11. Ratajczak J, Wysoczynski M, Hayek F, Janowska-Wieczorek A, Ratajczak MZ. Membrane-derived microvesicles: important and underappreciated mediators of cell-to-cell communication. Leukemia. 2006;20(9):1487-95.
12. Gastpar R, Gehrmann M, Bausero MA, Asea A, Gross C, Schroeder JA, Multhoff G. Heat shock protein 70 surface-positive tumor exosomes stimulate migratory and cytolytic activity of natural killer cells. Cancer Res. 2005;65(12):5238-47.
13. Cirone M, Di Renzo L, Lotti LV, Conte V, Trivedi P, Santarelli R, et al. Primary effusion lymphoma cell death induced by bortezomib and AG 490 activates dendritic cells through CD91. PLoS One. 2012;7(3):e31732.
14. Hedlund M, Nagaeva O, Kargl D, Baranov V, Mincheva-Nilsson L. Thermal- and oxidative stress causes enhanced release of NKG2D ligand-bearing immunosuppressive exosomes in leukemia/lymphoma T and B cells. PLoS One. 2011;6(2):e16899.
15. Hashemi SM, Hassan ZM, Soudi S, Ghazanfari T, Kheirandish M, Shahabi S. Evaluation of anti-tumor effects of tumor cell lysate enriched by HSP-70 against fibrosarcoma tumor in BALB/c mice. International immunopharmacology. 2007;7(7):920-7.
16. Shevtsov M, Multhoff G. Heat Shock Protein-Peptide and HSP-Based Immunotherapies for the Treatment of Cancer. Front Immunol. 2016;7:171.
17. Sherman MY, Gabai VL. Hsp70 in cancer: back to the future. Oncogene. 2015;34(32):4153-61.
18. Milani V, Noessner E, Ghose S, Kuppner M, Ahrens B, Scharner A, et al. Heat shock protein 70: role in antigen presentation and immune stimulation. Int J Hyperthermia. 2002;18(6):563-75.
19. He SB, Sun K, Wang L, Li DC, Zhang YY. [GM-CSF gene-modified dendritic cell vaccine enhances antitumor immunity in vitro]. Zhonghua Zhong Liu Za Zhi. 2010;32(6):410-4.
20. Wang HY, Fu JC, Lee YC, Lu PJ. Hyperthermia stress activates heat shock protein expression via propyl isomerase 1 regulation with heat shock factor 1. Mol Cell Biol. 2013;33(24):4889-99.
21. McNulty S, Colaco CA, Blandford LE, Bailey CR, Baschieri S, Todryk S. Heat-shock proteins as dendritic cell-targeting vaccines--getting warmer. Immunology. 2013;139(4):407-15.
22. Wronska AK, Bogus MI. Heat shock proteins (HSP 90, 70, 60, and 27) in Galleria mellonella (Lepidoptera) hemolymph are affected by infection with Conidiobolus coronatus (Entomophthorales). PLoS One. 2020;15(2):e0228556.
23. Zhu H, Fang X, Zhang D, Wu W, Shao M, Wang L, Gu J. Membrane-bound heat shock proteins facilitate the uptake of dying cells and cross-presentation of cellular antigen. Apoptosis. 2016;21(1):96-109.
24. Cho JA, Lee YS, Kim SH, Ko JK, Kim CW. MHC independent anti-tumor immune responses induced by Hsp70-enriched exosomes generate tumor regression in murine models. Cancer Lett. 2009;275(2):256-65.
25. Mirsanei Z, Habibi S, Kheshtchin N, Mirzaei R, Arab S, Zand B, et al. Optimized dose of dendritic cell-based vaccination in experimental model of tumor using artificial neural network. 2020:172-82.
26. Thery C, Zitvogel L, Amigorena S. Exosomes: composition, biogenesis and function. Nat Rev Immunol. 2002;2(8):569-79.
27. Heidari N, Abbasi-Kenarsari H, Namaki S, Baghaei K, Zali MR, Ghaffari Khaligh S, Hashemi SM. Adipose-derived mesenchymal stem cell-secreted exosome alleviates dextran sulfate sodium-induced acute colitis by Treg cell induction and inflammatory cytokine reduction. J Cell Physiol. 2021.
28. Wolfers J, Lozier A, Raposo G, Regnault A, Thery C, Masurier C, et al. Tumor-derived exosomes are a source of shared tumor rejection antigens for CTL cross-priming. Nat Med. 2001;7(3):297-303.
29. Reddy VS, Madala SK, Trinath J, Reddy GB. Extracellular small heat shock proteins: exosomal biogenesis and function. Cell Stress Chaperones. 2018;23(3):441-54.
30. Todryk SM, Gough MJ, Pockley AG. Facets of heat shock protein 70 show immunotherapeutic potential. Immunology. 2003;110(1):1-9.
31. Multhoff G, Botzler C, Wiesnet M, Muller E, Meier T, Wilmanns W, Issels RD. A stress-inducible 72-kDa heat-shock protein (HSP72) is expressed on the surface of human tumor cells, but not on normal cells. Int J Cancer. 1995;61(2):272-9.
32. Naseri M, Bozorgmehr M, Zoller M, Ranaei Pirmardan E, Madjd Z. Tumor-derived exosomes: the next generation of promising cell-free vaccines in cancer immunotherapy. Oncoimmunology. 2020;9(1):1779991.
33. Hauet-Broere F, Wieten L, Guichelaar T, Berlo S, van der Zee R, Van Eden W. Heat shock proteins induce T cell regulation of chronic inflammation. Ann Rheum Dis. 2006;65 Suppl 3:iii65-8.
34. Ferrarini M, Heltai S, Zocchi MR, Rugarli C. Unusual expression and localization of heat-shock proteins in human tumor cells. Int J Cancer. 1992;51(4):613-9.
35. Hao S, Bai O, Li F, Yuan J, Laferte S, Xiang J. Mature dendritic cells pulsed with exosomes stimulate efficient cytotoxic T-lymphocyte responses and antitumour immunity. Immunology. 2007;120(1):90-102.
36. Hsu DH, Paz P, Villaflor G, Rivas A, Mehta-Damani A, Angevin E, et al. Exosomes as a tumor vaccine: enhancing potency through direct loading of antigenic peptides. J Immunother. 2003;26(5):440-50.
| Files | ||
| Issue | Vol 23 No 1 (2024) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijaai.v23i1.14957 | |
| Keywords | ||
| Dendritic cell Exosome Heat-shock protein Tumor | ||
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How to Cite
1.
Heidari N, Abbasi-kenarsari H, Niknam B, Asadirad A, Amani D, Mirsanei Z, Hashemi SM. Exosomes Derived from Heat‐shocked Tumor Cells Promote In vitro Maturation of Bone Marrow-derived Dendritic Cells. Iran J Allergy Asthma Immunol. 2024;23(1):97-106.
