Cutting Edge: Delay and Reversal of T Cell Tolerance by Intratumoral Injection of Antigen-Loaded Dendritic Cells in an Autochthonous Tumor Model
The tumor environment exerts a powerful suppressive influence on infiltrating tumor-reactive T cells. It induces tolerance of adoptively transferred effector T cells as they enter tumors and maintains the tolerance of persisting tumor-infiltrating T cells. In an autochthonous prostate cancer model,...
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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/1721.1/73448 https://orcid.org/0000-0003-2398-5896 https://orcid.org/0000-0002-5687-6154 |
| _version_ | 1826196402375491584 |
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| author | Higham, Eileen M. Wittrup, Karl Dane Chen, Jianzhu Shen, Chase |
| 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 Shen, Chase |
| author_sort | Higham, Eileen M. |
| collection | MIT |
| description | The tumor environment exerts a powerful suppressive influence on infiltrating tumor-reactive T cells. It induces tolerance of adoptively transferred effector T cells as they enter tumors and maintains the tolerance of persisting tumor-infiltrating T cells. In an autochthonous prostate cancer model, in which tumor-reactive CD8 T cells are trackable, we demonstrate that both depletion of endogenous dendritic cells (DCs) and intratumoral injection of Ag-loaded mature DCs delayed the tolerization of tumor-infiltrating effector CD8 T cells. Intratumoral injection of Ag-loaded DCs also reactivated tolerized CD8 T cells in the tumor tissue. The observed effects lasted as long as the injected DCs persisted. These findings are consistent with a critical role of DCs in modulating T cell reactivity in the tumor environment. They also suggest new potential strategies to extend the functionality of transferred effector T cells and to restore function to tolerized tumor-infiltrating T cells for cancer immunotherapy. |
| first_indexed | 2024-09-23T10:26:16Z |
| format | Article |
| id | mit-1721.1/73448 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T10:26:16Z |
| publishDate | 2012 |
| publisher | The American Association of Immunologists |
| record_format | dspace |
| spelling | mit-1721.1/734482022-09-30T21:08:07Z Cutting Edge: Delay and Reversal of T Cell Tolerance by Intratumoral Injection of Antigen-Loaded Dendritic Cells in an Autochthonous Tumor Model Higham, Eileen M. Wittrup, Karl Dane Chen, Jianzhu Shen, Chase 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 Higham, Eileen M. Shen, Ching-Hung Wittrup, Karl Dane Chen, Jianzhu The tumor environment exerts a powerful suppressive influence on infiltrating tumor-reactive T cells. It induces tolerance of adoptively transferred effector T cells as they enter tumors and maintains the tolerance of persisting tumor-infiltrating T cells. In an autochthonous prostate cancer model, in which tumor-reactive CD8 T cells are trackable, we demonstrate that both depletion of endogenous dendritic cells (DCs) and intratumoral injection of Ag-loaded mature DCs delayed the tolerization of tumor-infiltrating effector CD8 T cells. Intratumoral injection of Ag-loaded DCs also reactivated tolerized CD8 T cells in the tumor tissue. The observed effects lasted as long as the injected DCs persisted. These findings are consistent with a critical role of DCs in modulating T cell reactivity in the tumor environment. They also suggest new potential strategies to extend the functionality of transferred effector T cells and to restore function to tolerized tumor-infiltrating T cells for cancer immunotherapy. National Science Foundation (U.S.) (Graduate Research Fellowship) National Institutes of Health (U.S.) (Grant CA100875) United States. Dept. of Defense (National Defense Science and Engineering Graduate Fellowship) David H. Koch Institute for Integrative Cancer Research at MIT (Research Fund) 2012-09-27T19:29:50Z 2012-09-27T19:29:50Z 2010-04 2010-01 Article http://purl.org/eprint/type/JournalArticle 0022-1767 1550-6606 http://hdl.handle.net/1721.1/73448 Higham, E. M. et al. “Cutting Edge: Delay and Reversal of T Cell Tolerance by Intratumoral Injection of Antigen-Loaded Dendritic Cells in an Autochthonous Tumor Model.” The Journal of Immunology 184.11 (2010): 5954–5958. https://orcid.org/0000-0003-2398-5896 https://orcid.org/0000-0002-5687-6154 en_US http://dx.doi.org/10.4049/jimmunol.1000265 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 Shen, Chase Cutting Edge: Delay and Reversal of T Cell Tolerance by Intratumoral Injection of Antigen-Loaded Dendritic Cells in an Autochthonous Tumor Model |
| title | Cutting Edge: Delay and Reversal of T Cell Tolerance by Intratumoral Injection of Antigen-Loaded Dendritic Cells in an Autochthonous Tumor Model |
| title_full | Cutting Edge: Delay and Reversal of T Cell Tolerance by Intratumoral Injection of Antigen-Loaded Dendritic Cells in an Autochthonous Tumor Model |
| title_fullStr | Cutting Edge: Delay and Reversal of T Cell Tolerance by Intratumoral Injection of Antigen-Loaded Dendritic Cells in an Autochthonous Tumor Model |
| title_full_unstemmed | Cutting Edge: Delay and Reversal of T Cell Tolerance by Intratumoral Injection of Antigen-Loaded Dendritic Cells in an Autochthonous Tumor Model |
| title_short | Cutting Edge: Delay and Reversal of T Cell Tolerance by Intratumoral Injection of Antigen-Loaded Dendritic Cells in an Autochthonous Tumor Model |
| title_sort | cutting edge delay and reversal of t cell tolerance by intratumoral injection of antigen loaded dendritic cells in an autochthonous tumor model |
| url | http://hdl.handle.net/1721.1/73448 https://orcid.org/0000-0003-2398-5896 https://orcid.org/0000-0002-5687-6154 |
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