Exosomes are small membrane vesicles secreted from various types of cells.
Tumor-derived exosomes contain
MHC class I molecules and
tumor-specific
antigens, receiving attention as a potential
cancer vaccine. For induction of efficient anti-
tumor immunity, CD4+ helper T cells are required, which recognize appropriate MHC class II-
peptide complexes. In this study, we have established an
MHC class II molecule-expressing B16F1 murine
melanoma cell line (B16F1- CIITA) by transduction of the CIITA (
Class II transactivator) gene. Exosomes from B16-CII cells (CIITA- Exo) contained a high amount of MHC class II as well as a
tumor antigen TRP2. When loaded on dendritic cells (DCs), CIITA-Exo induced the increased expression of
MHC class II molecules and CD86 than the exosomes from the parental cells (Exo). In vitro assays using co-culture of immunized splenocytes and exosome-loaded DCs demonstrated that CIITA-Exo enhanced the splenocyte proliferation and
IL-2 secretion. Consistently, compared to B16-Exo, CIITA-Exo induced the increased
mRNA levels of inflammatory
cytokines such as TNF-α,
chemokine receptor CCR7 and the production of Th1-polarizing
cytokine IL-12. A
tumor preventive model showed that CIITA-Exo significantly inhibited
tumor growth in a dose-dependent manner. Ex vivo assays using immunized mice demonstrated that CIITA-Exo induced a higher amount of Th1-polarized immune responses such as Th1-type
IgG2a antibodies and IFN-γ
cytokine as well as TRP2-specific CD8+ T cells. A
tumor therapeutic model delayed effects of
tumor growth by CIITA-Exo. These findings indicate that CIITA-Exo are more efficient as compared to parental Exo to induce anti-
tumor immune responses, suggesting a potential role of MHC class II-containing
tumor exosomes as an efficient
cancer vaccine.