Upregulated Expression of Indoleamine 2, 3-Dioxygenase in Primary Breast Cancer Correlates with Increase of Infiltrated Regulatory T Cells In Situ and Lymph Node Metastasis
IDO has been reported to induce immunotolerance and promote metastasis in solid malignancy, but the mechanisms involved were not fully understood. In this study, the expression of IDO in primary breast cancer was examined and the correlation between the expression levels of IDO and the densities of...
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| Format: | Article |
| Language: | English |
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Wiley
2011-01-01
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| Series: | Clinical and Developmental Immunology |
| Online Access: | http://dx.doi.org/10.1155/2011/469135 |
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| author | Jinpu Yu Jingyan Sun Shizhen Emily Wang Hui Li Shui Cao Yizi Cong Juntian Liu Xiubao Ren |
| author_facet | Jinpu Yu Jingyan Sun Shizhen Emily Wang Hui Li Shui Cao Yizi Cong Juntian Liu Xiubao Ren |
| author_sort | Jinpu Yu |
| collection | DOAJ |
| description | IDO has been reported to induce immunotolerance and promote metastasis in solid malignancy, but the mechanisms involved were not fully understood. In this study, the expression of IDO in primary breast cancer was examined and the correlation between the expression levels of IDO and the densities of Foxp3+ Tregs in situ was studied. The IDO stably-expressing CHO cells(IDO/CHO) were generated to evaluate the induction of Foxp3+ Tregs after coculturing with CD3+ T cells in vitro. The IDO expression in cancer was higher than that in benign diseases both at RNA and protein levels. The IDO expression was significantly upregulated in tumors of more advanced stages and with more extensive lymph node metastasis, and displayed positive linear correlation with the density of Foxp3+ Tregs. We further demonstrated that CD4+CD25+CD127− Tregs could be amplified by coculturing CD3+ T cells with IDO/CHO cells in vitro which displayed increasing Foxp3 expression both at mRNA and protein levels. Our results implied that up-regulation of IDO in primary breast cancer may inhibit local immune surveillance and promote metastasis by favoring development and infiltration of Foxp3+ Tregs in the tumor microenvironment. |
| format | Article |
| id | doaj-art-1d736225bf184446933d98af6fc8aeb0 |
| institution | Kabale University |
| issn | 1740-2522 1740-2530 |
| language | English |
| publishDate | 2011-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical and Developmental Immunology |
| spelling | doaj-art-1d736225bf184446933d98af6fc8aeb02025-02-03T05:51:49ZengWileyClinical and Developmental Immunology1740-25221740-25302011-01-01201110.1155/2011/469135469135Upregulated Expression of Indoleamine 2, 3-Dioxygenase in Primary Breast Cancer Correlates with Increase of Infiltrated Regulatory T Cells In Situ and Lymph Node MetastasisJinpu Yu0Jingyan Sun1Shizhen Emily Wang2Hui Li3Shui Cao4Yizi Cong5Juntian Liu6Xiubao Ren7Department of Immunology, Key Laboratory of Cancer Prevention and Therapy, Tianjin Cancer Institute & Hospital, Tianjin Medical University, Tianjin 300060, ChinaDepartment of Breast Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Cancer Institute & Hospital, Tianjin Medical University, Tianjin 300060, ChinaDivision of Tumor Cell Biology, Beckman Research Institute of City of Hope, Duarte, CA 91010, USADepartment of Immunology, Key Laboratory of Cancer Prevention and Therapy, Tianjin Cancer Institute & Hospital, Tianjin Medical University, Tianjin 300060, ChinaDepartment of Immunology, Key Laboratory of Cancer Prevention and Therapy, Tianjin Cancer Institute & Hospital, Tianjin Medical University, Tianjin 300060, ChinaDepartment of Breast Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Cancer Institute & Hospital, Tianjin Medical University, Tianjin 300060, ChinaDepartment of Breast Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Cancer Institute & Hospital, Tianjin Medical University, Tianjin 300060, ChinaDepartment of Immunology, Key Laboratory of Cancer Prevention and Therapy, Tianjin Cancer Institute & Hospital, Tianjin Medical University, Tianjin 300060, ChinaIDO has been reported to induce immunotolerance and promote metastasis in solid malignancy, but the mechanisms involved were not fully understood. In this study, the expression of IDO in primary breast cancer was examined and the correlation between the expression levels of IDO and the densities of Foxp3+ Tregs in situ was studied. The IDO stably-expressing CHO cells(IDO/CHO) were generated to evaluate the induction of Foxp3+ Tregs after coculturing with CD3+ T cells in vitro. The IDO expression in cancer was higher than that in benign diseases both at RNA and protein levels. The IDO expression was significantly upregulated in tumors of more advanced stages and with more extensive lymph node metastasis, and displayed positive linear correlation with the density of Foxp3+ Tregs. We further demonstrated that CD4+CD25+CD127− Tregs could be amplified by coculturing CD3+ T cells with IDO/CHO cells in vitro which displayed increasing Foxp3 expression both at mRNA and protein levels. Our results implied that up-regulation of IDO in primary breast cancer may inhibit local immune surveillance and promote metastasis by favoring development and infiltration of Foxp3+ Tregs in the tumor microenvironment.http://dx.doi.org/10.1155/2011/469135 |
| spellingShingle | Jinpu Yu Jingyan Sun Shizhen Emily Wang Hui Li Shui Cao Yizi Cong Juntian Liu Xiubao Ren Upregulated Expression of Indoleamine 2, 3-Dioxygenase in Primary Breast Cancer Correlates with Increase of Infiltrated Regulatory T Cells In Situ and Lymph Node Metastasis Clinical and Developmental Immunology |
| title | Upregulated Expression of Indoleamine 2, 3-Dioxygenase in Primary Breast Cancer Correlates with Increase of Infiltrated Regulatory T Cells In Situ and Lymph Node Metastasis |
| title_full | Upregulated Expression of Indoleamine 2, 3-Dioxygenase in Primary Breast Cancer Correlates with Increase of Infiltrated Regulatory T Cells In Situ and Lymph Node Metastasis |
| title_fullStr | Upregulated Expression of Indoleamine 2, 3-Dioxygenase in Primary Breast Cancer Correlates with Increase of Infiltrated Regulatory T Cells In Situ and Lymph Node Metastasis |
| title_full_unstemmed | Upregulated Expression of Indoleamine 2, 3-Dioxygenase in Primary Breast Cancer Correlates with Increase of Infiltrated Regulatory T Cells In Situ and Lymph Node Metastasis |
| title_short | Upregulated Expression of Indoleamine 2, 3-Dioxygenase in Primary Breast Cancer Correlates with Increase of Infiltrated Regulatory T Cells In Situ and Lymph Node Metastasis |
| title_sort | upregulated expression of indoleamine 2 3 dioxygenase in primary breast cancer correlates with increase of infiltrated regulatory t cells in situ and lymph node metastasis |
| url | http://dx.doi.org/10.1155/2011/469135 |
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