Exosomes Derived from Heat-shocked Tumor Cells Promote In vitro Maturation of Bone Marrow-derived Dendritic Cells.

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.