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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Main Authors: Jinpu Yu, Jingyan Sun, Shizhen Emily Wang, Hui Li, Shui Cao, Yizi Cong, Juntian Liu, Xiubao Ren
Format: Article
Language:English
Published: Wiley 2011-01-01
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.
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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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