CD8[superscript +] T-cell Responses Rapidly Select for Antigen-Negative Tumor Cells in the Prostate
Stimulation of patients' immune systems for the treatment of solid tumors is an emerging therapeutic paradigm. The use of enriched autologous T cells for adoptive cell therapy or vaccination with antigen-loaded dendritic cells have shown clinical efficacy in melanoma and prostate cancer, respec...
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| 格式: | 文件 |
| 语言: | en_US |
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American Association for Cancer Research
2014
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| 在线阅读: | http://hdl.handle.net/1721.1/91603 https://orcid.org/0000-0003-2398-5896 https://orcid.org/0000-0002-5687-6154 |
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| author | Bak, S. Peter G. Barnkob, Mike Stein Wittrup, Karl Dane Chen, Jianzhu |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Bak, S. Peter G. Barnkob, Mike Stein Wittrup, Karl Dane Chen, Jianzhu |
| author_sort | Bak, S. Peter G. |
| collection | MIT |
| description | Stimulation of patients' immune systems for the treatment of solid tumors is an emerging therapeutic paradigm. The use of enriched autologous T cells for adoptive cell therapy or vaccination with antigen-loaded dendritic cells have shown clinical efficacy in melanoma and prostate cancer, respectively. However, the long-term effects of immune responses on selection and outgrowth of antigen-negative tumor cells in specific tumor types must be determined to understand and achieve long-term therapeutic effects. In this study, we have investigated the expression of a tumor-specific antigen in situ after treatment with tumor-specific CD8[superscript +] T cells in an autochthonous mouse model of prostate cancer. After T-cell treatment, aggregates of dead antigen-positive tumor cells were concentrated in the lumen of the prostate gland and were eventually eliminated from the prostate tissue. Despite the elimination of antigen-positive tumor cells, prostate tumor continued to grow in T-cell–treated mice. Interestingly, the remaining tumor cells were antigen negative and downregulated MHC class I expression. These results show that CD8[superscript +] T cells are effective in eliminating antigen-bearing prostate tumor cells but they also can select for the outgrowth of antigen-negative tumor cells. These findings provide insights into the requirements for an effective cancer immunotherapy within the prostate that not only induces potent immune responses but also avoids selection and outgrowth of antigen-negative tumor cells. |
| first_indexed | 2024-09-23T12:26:58Z |
| format | Article |
| id | mit-1721.1/91603 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T12:26:58Z |
| publishDate | 2014 |
| publisher | American Association for Cancer Research |
| record_format | dspace |
| spelling | mit-1721.1/916032022-09-28T08:01:07Z CD8[superscript +] T-cell Responses Rapidly Select for Antigen-Negative Tumor Cells in the Prostate Bak, S. Peter G. Barnkob, Mike Stein 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 Bak, S. Peter G. Barnkob, Mike Stein Wittrup, Karl Dane Chen, Jianzhu Stimulation of patients' immune systems for the treatment of solid tumors is an emerging therapeutic paradigm. The use of enriched autologous T cells for adoptive cell therapy or vaccination with antigen-loaded dendritic cells have shown clinical efficacy in melanoma and prostate cancer, respectively. However, the long-term effects of immune responses on selection and outgrowth of antigen-negative tumor cells in specific tumor types must be determined to understand and achieve long-term therapeutic effects. In this study, we have investigated the expression of a tumor-specific antigen in situ after treatment with tumor-specific CD8[superscript +] T cells in an autochthonous mouse model of prostate cancer. After T-cell treatment, aggregates of dead antigen-positive tumor cells were concentrated in the lumen of the prostate gland and were eventually eliminated from the prostate tissue. Despite the elimination of antigen-positive tumor cells, prostate tumor continued to grow in T-cell–treated mice. Interestingly, the remaining tumor cells were antigen negative and downregulated MHC class I expression. These results show that CD8[superscript +] T cells are effective in eliminating antigen-bearing prostate tumor cells but they also can select for the outgrowth of antigen-negative tumor cells. These findings provide insights into the requirements for an effective cancer immunotherapy within the prostate that not only induces potent immune responses but also avoids selection and outgrowth of antigen-negative tumor cells. American Cancer Society (Postdoctoral Fellowship 12109-PF-11-025-01-LIB) John D. Proctor Foundation (Margaret A. Cunningham Immune Mechanisms in Cancer Research Fellowship) United States. Army Medical Research and Materiel Command (Prostate Cancer Research Program Grant) National Cancer Institute (U.S.) (Koch Institute Support (Core) Grant P30-CA14051) 2014-11-17T20:09:53Z 2014-11-17T20:09:53Z 2013-09 2013-09 Article http://purl.org/eprint/type/JournalArticle 2326-6066 2326-6074 http://hdl.handle.net/1721.1/91603 Bak, S. P., M. S. Barnkob, K. D. Wittrup, and J. Chen. “CD8+ T-Cell Responses Rapidly Select for Antigen-Negative Tumor Cells in the Prostate.” Cancer Immunology Research 1, no. 6 (December 1, 2013): 393–401. https://orcid.org/0000-0003-2398-5896 https://orcid.org/0000-0002-5687-6154 en_US http://dx.doi.org/10.1158/2326-6066.cir-13-0109 Cancer Immunology Research Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf American Association for Cancer Research PMC |
| spellingShingle | Bak, S. Peter G. Barnkob, Mike Stein Wittrup, Karl Dane Chen, Jianzhu CD8[superscript +] T-cell Responses Rapidly Select for Antigen-Negative Tumor Cells in the Prostate |
| title | CD8[superscript +] T-cell Responses Rapidly Select for Antigen-Negative Tumor Cells in the Prostate |
| title_full | CD8[superscript +] T-cell Responses Rapidly Select for Antigen-Negative Tumor Cells in the Prostate |
| title_fullStr | CD8[superscript +] T-cell Responses Rapidly Select for Antigen-Negative Tumor Cells in the Prostate |
| title_full_unstemmed | CD8[superscript +] T-cell Responses Rapidly Select for Antigen-Negative Tumor Cells in the Prostate |
| title_short | CD8[superscript +] T-cell Responses Rapidly Select for Antigen-Negative Tumor Cells in the Prostate |
| title_sort | cd8 superscript t cell responses rapidly select for antigen negative tumor cells in the prostate |
| url | http://hdl.handle.net/1721.1/91603 https://orcid.org/0000-0003-2398-5896 https://orcid.org/0000-0002-5687-6154 |
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