In vivo therapeutic effects of colorectal cancer cell-derived exosomes

Exosomes are nano-sized structures with lipid bilayer membranes that can be secreted by cancer cells. They play an important role in the biology of the tumor extracellular matrix. Exosomes may contain and transfer tumor antigens to dendritic cells to trigger T cell-mediated anti-tumor immune responses. BALB/c mice bearing CT26 colorectal cancer were treated subcutaneously with purified exosomes from analogous tumor cells. The mice were analyzed with respect to tumor size, survival, and anti-tumor immunity responses, including gene expression of cytokines and flowcytometry analysis of T lymphocytes. The rate of tumor size growth in the exosome-treated group significantly decreased (p <0.05), and the flow cytometry results showed a significant reduction in the spleen regulatory T cells (Tregs) count of the exosome-treated group, compared with the untreated group (P=0.02). Although the increase in the serum level of interferon-γ (IFN-γ) and the number of cytotoxic CD8 T lymphocytes (CTLs) in the spleen tissue was not significant (P>0.05), the gene expression of IFN-γ increased significantly (P=0.006). The present results revealed that subcutaneous administration of tumor-derived exosomes could effectively lead to the inhibition of tumor progression by decreasing the number of Treg cells and up-regulation of the IFN-γ gene. Therefore, tumor-derived exosomes can be used as potential vaccines in cancer immunotherapy.