Chemotherapy-Associated Extracellular Vesicles Modulate T Cells Activity and Cytokine Release

Colorectal cancer (CRC) remains one of the most widely diagnosed cancers worldwide. Despite the advances in medical research, there is still a lot to be explored between cancer cells and the tumor microenvironment, namely immune cells. Extracellular vesicles (EVs) have been shown to mediate communication between cells and can modulate the activity of immune cells. External stimuli such as stress and chemotherapy can influence the activity of the released EVs. Nevertheless, the relationship between chemotherapy, EVs and immune cells has yet to be fully explored. In this study, we aimed to elucidate the immune-related functional mechanisms of EVs isolated from pre- and post- FOLFOX chemotherapy from CRC patients. The EVs were isolated from the serum of matched patients and characterized via dynamic light scattering. The EVs were then co-incubated with primary CD8 T cells isolated from healthy donors and Jurkat cells. The apoptosis, cell cycle profile, gene expression and cytokines were evaluated. Upon treatment with EVs, the T cells underwent apoptosis however no differences were seen in the cell cycle phases. Gene expression related to cytokine release was also differentially expressed namely IRF4. The level of cytokines that were released also differed between the two groups. Our study has shown that there are some minor differences in the activity of the EVs after induction with chemotherapy.