The immune system strikes back: cellular immune responses against indoleamine 2,3-dioxygenase.
<h4>Background</h4>The enzyme indoleamine 2,3-dioxygenase (IDO) exerts an well established immunosuppressive function in cancer. IDO is expressed within the tumor itself as well as in antigen-presenting cells in tumor-draining lymph nodes, where it promotes the establishment of periphera...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2009-09-01
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| Series: | PLoS ONE |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19738905/?tool=EBI |
| _version_ | 1818682094808727552 |
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| author | Rikke Baek Sørensen Linda Berge-Hansen Niels Junker Christina Aaen Hansen Sine Reker Hadrup Ton N M Schumacher Inge Marie Svane Jürgen C Becker Per thor Straten Mads Hald Andersen |
| author_facet | Rikke Baek Sørensen Linda Berge-Hansen Niels Junker Christina Aaen Hansen Sine Reker Hadrup Ton N M Schumacher Inge Marie Svane Jürgen C Becker Per thor Straten Mads Hald Andersen |
| author_sort | Rikke Baek Sørensen |
| collection | DOAJ |
| description | <h4>Background</h4>The enzyme indoleamine 2,3-dioxygenase (IDO) exerts an well established immunosuppressive function in cancer. IDO is expressed within the tumor itself as well as in antigen-presenting cells in tumor-draining lymph nodes, where it promotes the establishment of peripheral immune tolerance to tumor antigens. In the present study, we tested the notion whether IDO itself may be subject to immune responses.<h4>Methods and findings</h4>The presence of naturally occurring IDO-specific CD8 T cells in cancer patients was determined by MHC/peptide stainings as well as ELISPOT. Antigen specific cytotoxic T lymphocytes (CTL) from the peripheral blood of cancer patients were cloned and expanded. The functional capacity of the established CTL clones was examined by chrome release assays. The study unveiled spontaneous cytotoxic T-cell reactivity against IDO in peripheral blood as well as in the tumor microenvironment of different cancer patients. We demonstrate that these IDO reactive T cells are indeed peptide specific, cytotoxic effector cells. Hence, IDO reactive T cells are able to recognize and kill tumor cells including directly isolated AML blasts as well as IDO-expressing dendritic cells, i.e. one of the major immune suppressive cell populations.<h4>Conclusion</h4>IDO may serve as an important and widely applicable target for anti-cancer immunotherapeutic strategies. Furthermore, as emerging evidence suggests that IDO constitutes a significant counter-regulatory mechanism induced by pro-inflammatory signals, IDO-based immunotherapy holds the promise to boost anti-cancer immunotherapy in general. |
| first_indexed | 2024-12-17T10:13:23Z |
| format | Article |
| id | doaj.art-0a4acef351204000938334c36f4305e9 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-17T10:13:23Z |
| publishDate | 2009-09-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-0a4acef351204000938334c36f4305e92022-12-21T21:52:58ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-09-0149e691010.1371/journal.pone.0006910The immune system strikes back: cellular immune responses against indoleamine 2,3-dioxygenase.Rikke Baek SørensenLinda Berge-HansenNiels JunkerChristina Aaen HansenSine Reker HadrupTon N M SchumacherInge Marie SvaneJürgen C BeckerPer thor StratenMads Hald Andersen<h4>Background</h4>The enzyme indoleamine 2,3-dioxygenase (IDO) exerts an well established immunosuppressive function in cancer. IDO is expressed within the tumor itself as well as in antigen-presenting cells in tumor-draining lymph nodes, where it promotes the establishment of peripheral immune tolerance to tumor antigens. In the present study, we tested the notion whether IDO itself may be subject to immune responses.<h4>Methods and findings</h4>The presence of naturally occurring IDO-specific CD8 T cells in cancer patients was determined by MHC/peptide stainings as well as ELISPOT. Antigen specific cytotoxic T lymphocytes (CTL) from the peripheral blood of cancer patients were cloned and expanded. The functional capacity of the established CTL clones was examined by chrome release assays. The study unveiled spontaneous cytotoxic T-cell reactivity against IDO in peripheral blood as well as in the tumor microenvironment of different cancer patients. We demonstrate that these IDO reactive T cells are indeed peptide specific, cytotoxic effector cells. Hence, IDO reactive T cells are able to recognize and kill tumor cells including directly isolated AML blasts as well as IDO-expressing dendritic cells, i.e. one of the major immune suppressive cell populations.<h4>Conclusion</h4>IDO may serve as an important and widely applicable target for anti-cancer immunotherapeutic strategies. Furthermore, as emerging evidence suggests that IDO constitutes a significant counter-regulatory mechanism induced by pro-inflammatory signals, IDO-based immunotherapy holds the promise to boost anti-cancer immunotherapy in general.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19738905/?tool=EBI |
| spellingShingle | Rikke Baek Sørensen Linda Berge-Hansen Niels Junker Christina Aaen Hansen Sine Reker Hadrup Ton N M Schumacher Inge Marie Svane Jürgen C Becker Per thor Straten Mads Hald Andersen The immune system strikes back: cellular immune responses against indoleamine 2,3-dioxygenase. PLoS ONE |
| title | The immune system strikes back: cellular immune responses against indoleamine 2,3-dioxygenase. |
| title_full | The immune system strikes back: cellular immune responses against indoleamine 2,3-dioxygenase. |
| title_fullStr | The immune system strikes back: cellular immune responses against indoleamine 2,3-dioxygenase. |
| title_full_unstemmed | The immune system strikes back: cellular immune responses against indoleamine 2,3-dioxygenase. |
| title_short | The immune system strikes back: cellular immune responses against indoleamine 2,3-dioxygenase. |
| title_sort | immune system strikes back cellular immune responses against indoleamine 2 3 dioxygenase |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19738905/?tool=EBI |
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