Exosomes from Dendritic Cells Loaded with Chaperone-Rich Cell Lysates Elicit a Potent T Cell Immune Response Against Intracranial Glioma in Mice
Autor: | Shuqin Zhan, Li Yao, Ning Bu, Huqing Wang, Hong Sun, Yun Du, Ru Zhang, Hai-qin Wu, Guilian Zhang |
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Rok vydání: | 2015 |
Předmět: |
endocrine system
medicine.medical_treatment T cell chemical and pharmacologic phenomena Biology Exosomes Mice Phosphatidylinositol 3-Kinases Cellular and Molecular Neuroscience Immune system Cell Line Tumor polycyclic compounds medicine Animals Cytotoxic T cell Proto-Oncogene Proteins c-cbl Heat-Shock Proteins B cell Brain Neoplasms Cell growth Dendritic Cells Glioma General Medicine Immunotherapy Molecular biology Mice Inbred C57BL medicine.anatomical_structure Cell culture Cancer research Female Proto-Oncogene Proteins c-akt hormones hormone substitutes and hormone antagonists CD8 Signal Transduction T-Lymphocytes Cytotoxic |
Zdroj: | Journal of Molecular Neuroscience. 56:631-643 |
ISSN: | 1559-1166 0895-8696 |
DOI: | 10.1007/s12031-015-0506-9 |
Popis: | Chaperone-rich cell lysates (CRCLs) may play an important role in the development of anti-tumor vaccines. Tumor-derived CRCLs have been reported to activate dendritic cells (DCs) to elicit potent anti-tumor activity. However, the role of DC-derived exosomes (DEXs) secreted from DCs loaded with CRCLs in the treatment of tumors has not been clearly determined. In the present study, DEXs were generated from DCs loaded with CRCLs derived from GL261 glioma cells. These DEXs, designated DEX (CRCL-GL261), were then used to treat DCs to create DEX (CRCL-GL261)-DCs. The DEX (CRCL-GL261)-DCs were found to promote cell proliferation and cytotoxic T lymphocyte (CTL) activity of CD4(+) and CD8(+) T cells in vitro compared with DEX (GL261)-DCs, which were loaded with DEXs derived from DCs loaded with GL261 tumor cell lysates. DEX (CRCL-GL261)-DCs significantly prolonged the survival of mice with tumors and inhibited tumor growth in vivo. In addition, DEX (CRCL-GL261)-DCs induced enhanced T cell infiltration in intracranial glioma tissues compared with other treatments. DEX (CRCL-GL261)-DCs induced strong production of anti-tumor cytokines, including interleukin-2 and interferon-γ. Moreover, depletion of CD4(+) and CD8(+) T cells significantly impaired the anti-tumor effect of DEX (CRCL-GL261)-DCs. Finally, DEX (CRCL-GL261)-DCs were found to negatively regulate Casitas B cell lineage lymphoma (Cbl)-b and c-Cbl signaling, leading to the activation of phosphatidyl inositol 3-kinase (PI3K)/Akt and extracellular signal-regulated kinase (ERK) signaling in T cells. In summary, we present evidence that DEX (CRCL-GL261)-DCs induce more potent and effective anti-tumor T cell immune responses and delineate the underlying mechanism by which DEX (CRCL-GL261)-DCs exerted their anti-tumor activity through modulating Cbl-b and c-Cbl signaling. These results provide novel and promising insight for the development of an anti-tumor vaccine. |
Databáze: | OpenAIRE |
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