Introduction of the CIITA gene into tumor cells produces exosomes with enhanced anti-tumor effects
Experimental & Molecular Medicine
;
: 281-290, 2011.
Article
in English
| WPRIM
| ID: wpr-19498
ABSTRACT
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-alpha, 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-gamma 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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Transduction, Genetic
/
Dendritic Cells
/
Melanoma, Experimental
/
Nuclear Proteins
/
Lymphocyte Activation
/
T-Lymphocytes
/
Survival Analysis
/
Trans-Activators
/
Gene Expression Regulation
/
Gene Transfer Techniques
Type of study:
Prognostic study
Limits:
Animals
Language:
English
Journal:
Experimental & Molecular Medicine
Year:
2011
Type:
Article
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