Antitumor Effects of Tumor-Derived Exosomes in Murine Hepatocellular Carcinoma Models.

[BACKGROUND] Exosomes (EXOs) are small vesicles derived from endosomes and secreted by most living cells including tumor cells. In recent years, these vesicles have been recognized as key mediators of intercellular communication, playing essential roles in the regulation and orchestration of diverse physiological and pathological processes within the organism.

[OBJECTIVE] To further investigate hepatocellular carcinoma (HCC)-derived exosomes containing tumor-associated antigens and to evaluate their immunostimulatory capacity and antitumor effects using in vitro and in vivo approaches.

[METHODS] Following isolation from tumor cells, exosomes were characterized and subsequently co-cultured with dendritic cells (DCs). The expression of surface molecules associated with DC maturation was then assessed using flow cytometry. A mouse liver cancer model was established and animals were randomly assigned to three groups: a negative control group (treated with PBS), an iDC group, and a DC-TEXs (tumor-derived exosomes) group. Tumor volume was monitored in all groups, with a focus on changes in immune cell populations and cytokine levels.

[RESULTS] Our in vitro studies showed that Hepa1-6 cell-derived EXOs dose-dependently enhanced dendritic cell (DC) maturation, as evidenced by increased expression of surface MHC-II molecules, co-stimulatory markers (CD40, CD80, CD86), and the maturation marker CD83. In vivo studies using subcutaneous HCC mouse models demonstrated that TEX administration significantly alters the tumor immune microenvironment, mainly through increased T lymphocyte infiltration and proliferation.

[CONCLUSION] Our results suggest that TEXs can serve as endogenous immunotherapeutic agents by eliciting tumor-specific T lymphocyte responses through DC activation cascades. These findings provide novel insights into the therapeutic exploitation of tumor-derived vesicles for the treatment of hepatocellular carcinoma.