CD8+ T Cell Priming by Dendritic Cell Vaccines Requires Antigen Transfer to Endogenous Antigen Presenting Cells
Autor: | Nina Bhardwaj, A. Yewdall, Felecia Jinwala, Scott B. Drutman, Keith S. Bahjat |
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Jazyk: | angličtina |
Rok vydání: | 2010 |
Předmět: |
Antigen presentation
Immunology/Innate Immunity Immunology/Immunomodulation Priming (immunology) lcsh:Medicine Antigen-Presenting Cells Biology CD8-Positive T-Lymphocytes Major histocompatibility complex Mice Immune system Antigen Cytotoxic T cell Animals Antigen-presenting cell lcsh:Science Mice Knockout Vaccines Multidisciplinary lcsh:R Dendritic cell Dendritic Cells Immunology Immunology/Immune Response biology.protein lcsh:Q Research Article |
Zdroj: | PLoS ONE PLoS ONE, Vol 5, Iss 6, p e11144 (2010) |
ISSN: | 1932-6203 |
Popis: | Background: Immunotherapeutic strategies to stimulate anti-tumor immunity are promising approaches for cancer treatment. A major barrier to their success is the immunosuppressive microenvironment of tumors, which inhibits the functions of endogenous dendritic cells (DCs) that are necessary for the generation of anti-tumor CD8+ T cells. To overcome this problem, autologous DCs are generated ex vivo, loaded with tumor antigens, and activated in this non-suppressive environment before administration to patients. However, DC-based vaccines rarely induce tumor regression. Methodology/Principal Findings: We examined the fate and function of these DCs following their injection using murine models, in order to better understand their interaction with the host immune system. Contrary to previous assumptions, we show that DC vaccines have an insignificant role in directly priming CD8+ T cells, but instead function primarily as vehicles for transferring antigens to endogenous antigen presenting cells, which are responsible for the subsequent activation of T cells. Conclusions/Significance: This reliance on endogenous immune cells may explain the limited success of current DC vaccines to treat cancer and offers new insight into how these therapies can be improved. Future approaches should focus on creating DC vaccines that are more effective at directly priming T cells, or abrogating the tumor induced suppression of endogenous DCs. |
Databáze: | OpenAIRE |
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