CD8+ T cell priming by dendritic cell vaccines requires antigen transfer to endogenous antigen presenting cells.
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...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2010-06-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2886840?pdf=render |
| _version_ | 1818336393646047232 |
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| author | Alice W Yewdall Scott B Drutman Felecia Jinwala Keith S Bahjat Nina Bhardwaj |
| author_facet | Alice W Yewdall Scott B Drutman Felecia Jinwala Keith S Bahjat Nina Bhardwaj |
| author_sort | Alice W Yewdall |
| collection | DOAJ |
| description | 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.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.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. |
| first_indexed | 2024-12-13T14:38:37Z |
| format | Article |
| id | doaj.art-46912c75a9b54ebc874d3c405e09a90d |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T14:38:37Z |
| publishDate | 2010-06-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-46912c75a9b54ebc874d3c405e09a90d2022-12-21T23:41:39ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-06-0156e1114410.1371/journal.pone.0011144CD8+ T cell priming by dendritic cell vaccines requires antigen transfer to endogenous antigen presenting cells.Alice W YewdallScott B DrutmanFelecia JinwalaKeith S BahjatNina BhardwajImmunotherapeutic 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.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.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.http://europepmc.org/articles/PMC2886840?pdf=render |
| spellingShingle | Alice W Yewdall Scott B Drutman Felecia Jinwala Keith S Bahjat Nina Bhardwaj CD8+ T cell priming by dendritic cell vaccines requires antigen transfer to endogenous antigen presenting cells. PLoS ONE |
| title | CD8+ T cell priming by dendritic cell vaccines requires antigen transfer to endogenous antigen presenting cells. |
| title_full | CD8+ T cell priming by dendritic cell vaccines requires antigen transfer to endogenous antigen presenting cells. |
| title_fullStr | CD8+ T cell priming by dendritic cell vaccines requires antigen transfer to endogenous antigen presenting cells. |
| title_full_unstemmed | CD8+ T cell priming by dendritic cell vaccines requires antigen transfer to endogenous antigen presenting cells. |
| title_short | CD8+ T cell priming by dendritic cell vaccines requires antigen transfer to endogenous antigen presenting cells. |
| title_sort | cd8 t cell priming by dendritic cell vaccines requires antigen transfer to endogenous antigen presenting cells |
| url | http://europepmc.org/articles/PMC2886840?pdf=render |
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