Activation of tolerogenic dendritic cells in the tumor draining lymph CD8+ T cells engineered to express CD40 ligand
Tolerogenic dendritic cells in the tumor microenvironment can inhibit the generation and maintenance of robust antitumor T cell responses. In this study, we investigated the effects of local delivery of CD40L by tumor-reactive CD8[supersript +] T cells on dendritic cell activation and antitumor T ce...
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| Format: | Article |
| Language: | en_US |
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The American Association of Immunologists
2012
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| Online Access: | http://hdl.handle.net/1721.1/72611 https://orcid.org/0000-0003-2398-5896 https://orcid.org/0000-0002-5687-6154 |
| _version_ | 1826206232088674304 |
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| author | Higham, Eileen M. Wittrup, Karl Dane Chen, Jianzhu |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Higham, Eileen M. Wittrup, Karl Dane Chen, Jianzhu |
| author_sort | Higham, Eileen M. |
| collection | MIT |
| description | Tolerogenic dendritic cells in the tumor microenvironment can inhibit the generation and maintenance of robust antitumor T cell responses. In this study, we investigated the effects of local delivery of CD40L by tumor-reactive CD8[supersript +] T cells on dendritic cell activation and antitumor T cell responses in the TRAMP model. To increase the immunostimulatory signal, CD40L was engineered, by deleting the majority of the cytoplasmic domain, to increase its levels of expression and duration on the surface of CD8[supersript +] T cells. Tumor-reactive CD8[supersript +] T cells expressing the truncated form of CD40L stimulated maturation of dendritic cells in vitro and in the prostate draining lymph nodes in vivo. Following dendritic cell maturation, a significantly higher fraction of adoptively transferred, tumor-reactive (reporter) CD8[supersript +] T cells was stimulated to express IFN-γ and infiltrate the prostate tissue. The antitumor CD8[supersript +] T cell response was further enhanced if TRAMP mice were also immunized with a tumor-specific Ag. These findings demonstrate that augmented T cell responses can be achieved by engineering tumor-reactive T cells to deliver stimulatory signals to dendritic cells in the tumor microenvironment. |
| first_indexed | 2024-09-23T13:26:11Z |
| format | Article |
| id | mit-1721.1/72611 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T13:26:11Z |
| publishDate | 2012 |
| publisher | The American Association of Immunologists |
| record_format | dspace |
| spelling | mit-1721.1/726112022-09-28T14:10:40Z Activation of tolerogenic dendritic cells in the tumor draining lymph CD8+ T cells engineered to express CD40 ligand Higham, Eileen M. Wittrup, Karl Dane Chen, Jianzhu Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Biology Massachusetts Institute of Technology. Department of Chemical Engineering Koch Institute for Integrative Cancer Research at MIT Chen, Jianzhu Higham, Eileen M. Wittrup, Karl Dane Chen, Jianzhu Tolerogenic dendritic cells in the tumor microenvironment can inhibit the generation and maintenance of robust antitumor T cell responses. In this study, we investigated the effects of local delivery of CD40L by tumor-reactive CD8[supersript +] T cells on dendritic cell activation and antitumor T cell responses in the TRAMP model. To increase the immunostimulatory signal, CD40L was engineered, by deleting the majority of the cytoplasmic domain, to increase its levels of expression and duration on the surface of CD8[supersript +] T cells. Tumor-reactive CD8[supersript +] T cells expressing the truncated form of CD40L stimulated maturation of dendritic cells in vitro and in the prostate draining lymph nodes in vivo. Following dendritic cell maturation, a significantly higher fraction of adoptively transferred, tumor-reactive (reporter) CD8[supersript +] T cells was stimulated to express IFN-γ and infiltrate the prostate tissue. The antitumor CD8[supersript +] T cell response was further enhanced if TRAMP mice were also immunized with a tumor-specific Ag. These findings demonstrate that augmented T cell responses can be achieved by engineering tumor-reactive T cells to deliver stimulatory signals to dendritic cells in the tumor microenvironment. National Defense Science and Engineering Graduate Fellowship (NSF) National Science Foundation (U.S.). Graduate Research Fellowship Program David H. Koch Cancer Research Fund National Institutes of Health (U.S.) (Grant number CA100875) National Institutes of Health (U.S.) (Grant number CA97296) 2012-09-11T14:58:23Z 2012-09-11T14:58:23Z 2010-03 2009-09 Article http://purl.org/eprint/type/JournalArticle 0022-1767 1550-6606 http://hdl.handle.net/1721.1/72611 Higham, E. M., K. D. Wittrup, and J. Chen. “Activation of Tolerogenic Dendritic Cells in the Tumor Draining Lymph Nodes by CD8+ T Cells Engineered to Express CD40 Ligand.” The Journal of Immunology 184.7 (2010): 3394–3400. https://orcid.org/0000-0003-2398-5896 https://orcid.org/0000-0002-5687-6154 en_US http://dx.doi.org/10.4049/jimmunol.0903111 Journal of Immunology Creative Commons Attribution-Noncommercial-Share Alike 3.0 http://creativecommons.org/licenses/by-nc-sa/3.0/ application/pdf The American Association of Immunologists PMC |
| spellingShingle | Higham, Eileen M. Wittrup, Karl Dane Chen, Jianzhu Activation of tolerogenic dendritic cells in the tumor draining lymph CD8+ T cells engineered to express CD40 ligand |
| title | Activation of tolerogenic dendritic cells in the tumor draining lymph CD8+ T cells engineered to express CD40 ligand |
| title_full | Activation of tolerogenic dendritic cells in the tumor draining lymph CD8+ T cells engineered to express CD40 ligand |
| title_fullStr | Activation of tolerogenic dendritic cells in the tumor draining lymph CD8+ T cells engineered to express CD40 ligand |
| title_full_unstemmed | Activation of tolerogenic dendritic cells in the tumor draining lymph CD8+ T cells engineered to express CD40 ligand |
| title_short | Activation of tolerogenic dendritic cells in the tumor draining lymph CD8+ T cells engineered to express CD40 ligand |
| title_sort | activation of tolerogenic dendritic cells in the tumor draining lymph cd8 t cells engineered to express cd40 ligand |
| url | http://hdl.handle.net/1721.1/72611 https://orcid.org/0000-0003-2398-5896 https://orcid.org/0000-0002-5687-6154 |
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