Introduction of theCIITAgene into tumor cells produces exosomes with enhanced anti-tumor effects
| Autor: | Jung Ah Cho, Yeong Shin Lee, Soohyun Kim, Chul Woo Kim |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
T-Lymphocytes
Clinical Biochemistry Melanoma Experimental chemical and pharmacologic phenomena C-C chemokine receptor type 7 Exosomes Lymphocyte Activation Cancer Vaccines Biochemistry Mice Antigen Transduction Genetic Cell Line Tumor MHC class I CIITA Animals Molecular Biology Cell Proliferation Immunity Cellular MHC class II biology Gene Transfer Techniques Nuclear Proteins Dendritic Cells MHC restriction Survival Analysis Tumor antigen Immunity Humoral Mice Inbred C57BL Gene Expression Regulation Trans-Activators biology.protein Cancer research Molecular Medicine Original Article Immunotherapy CD8 |
| Zdroj: | Experimental and Molecular Medicine. 43:281 |
| ISSN: | 1226-3613 |
| DOI: | 10.3858/emm.2011.43.5.029 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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