Involvement of MM cell-derived exosomes in T lymphocytes immune responses.

Exosomes were reported to mediate cell communication in the tumor microenvironment; however, the effects of multiple myeloma (MM)-derived exosomes on the quantity and function of T cells remain unknown. Exosomes were extracted from MM cell lines (OPM2 and U266B1) by ultracentrifugation using a Total Exosome Isolation kit. Exosomes were co-cultured with CD4+ T, CD8+ T and regulatory T (Treg) cells that were isolated from healthy donors (HDs) and patients with MM using magnetic beads. Flow cytometry was used to detect T cells apoptosis and expression of perforin and granzyme B in CD8+ T cells. Cell viability was detected using Cell Counting kit-8, and interleukin 10 (IL-10) and transforming growth factor beta (TGF-beta) in cell supernatants were detected by ELISA. The apoptosis of HD-CD4+ T was higher in the OPM2 group, and viability in the U266B1 group was decreased. The apoptosis of HD-CD8+ T decreased in the OPM2 and U266B1 groups, and cell viability increased in the OPM2 and the U266B1 groups. Perforin of HD-CD8+ T in the U266B1 group was lower while perforin of MM-CD8+ T in OPM2 and U266B1 groups was markedly decreased. The apoptosis of HD-Treg was lower in the U266B1 group, but apoptosis of MM-Treg was higher in the U266B1 group. The viability of HD-Treg in U266B1 group increased but the viability of MM-Treg in OPM2 and U266B1 groups decreased. TGF-beta from MM-Treg decreased in the OPM2 and U266B1 groups when compared with the control group (P<0.05). MM-derived exosomes promote apoptosis and inhibit proliferation of HD-CD4+ T, inhibit apoptosis and promote proliferation, but inhibit perforin of HD-CD8+ T, inhibit apoptosis and promote proliferation HD-Treg, and inhibit perforin of MM-CD8+ T and TGF-beta secretion of MM-Treg.