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 Mahmoud Hashemi

doi:10.18502/ijaai.v23i1.14957

Neda Heidari Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Hajar Abbasi-kenarsari Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Bahare Niknam Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Ali Asadirad Department of Immunology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
Davar Amani Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Zahra Mirsanei Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Seyed Mahmoud Hashemi Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

DOI: https://doi.org/10.18502/ijaai.v23i1.14957

Keywords: Dendritic cell; Exosome; Heat-shock protein; Tumor

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.