3620

IDO1

indoleamine 2,3-dioxygenase 1;IDO1;indoleamine 2,3-dioxygenase 1

indolamine 2,3 dioxygenase|indole 2,3-dioxygenase|indoleamine-pyrrole 2,3-dioxygenase

8p12-p11

protein-coding

OBJECTIVE: To investigate the expression of indoleamine 2, 3-dioxygenase (IDO) in breast cancer and its correlation with clinicopathologic factors and prognosis. METHODS: The expression of IDO, CD31, CD105 proteins in 40 specimens of breast cancer were assessed by immunohistochemistry. RESULTS: The overexpression rate of IDO in breast cancer was 67.5% (27/40), and expression of IDO was closely associated with clinical stage and lymph nodes metastasis. The disease-free survival rate in patients with IDO overexpression was not significantly lower than that in patients with negative or low expression of IDO (P > 0.05). Moreover, the expression of IDO was positively correlated with CD105-labeled microvessel density (r = 0.659, P < 0.05). CONCLUSIONS: expression of IDO is associated with clinical stage and lymph nodes metastasis, and microvessel densitty. IDO expression may promote the growth and metastasis of breast cancer, probably via the increased agiogenesis. A larger sample study is needed to verify whether the prognosis of beast cancer is significantly correlated with IDO expression.

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.

The mechanism by which malignant melanoma (MM) cells survive in lymph nodes is poorly understood. One possible mechanism by which MM cells can escape immune surveillance is through upregulation of immunomodulatory enzymes such as indoleamine 2,3-dioxygenase (IDO). In this study, 25 cases of MM lymph node metastases from patients with long and short survival were evaluated for expression of IDO and the number of Forkhead box p3 (FOXP3)-expressing regulatory T cells. Moderate to strong cytoplasmic IDO expression was present in all (15/15) MM lymph node metastases in patients with poor survival. Eight of 10 patients with metastatic MM and long survival were negative or only weakly positive for IDO. Upregulation of IDO in metastatic MM cells was associated with an increased number of regulatory T cells (Tregs). There was a statistically significant association between shorter survival and both a stronger IDO expression (p = 0.0019) and a higher number of FOXP3 expressing Tregs (p < 0.001). Using RT-PCR analysis, we showed that IDO expression in MM cells is induced by interferon-gamma. These data support the notion that metastatic MM cells select for expression of IDO to evade immunologic detection. Therefore, inhibition of IDO in MM patients may be a useful treatment strategy.

The abnormal distributions of memory T cells (Tm) and dendritic cells (DC) in stomach cancer are not well understood. Indoleamine 2,3-dioxygenase (IDO), produced by DC, may be an important enzyme affecting function and proliferation of Tm. In this study, IDO expression was examined by immunohistochemical staining. The subsets of Tm and DC were counted by flow cytometry. The percentages of CD4 + Tm and CD4 + central Tm (Tcm) were lower in tumor tissues than in normal tissues (P < 0.05), while the CD4 + effector Tm (Tem) and CD8 + Tem percentages were higher in tumor tissues (P < 0.05). The ratio of myeloid DC (DC1)/plasmacytoid DC (DC2) was significantly lower in tumor tissues (P = 0.009). The high expression of IDO was more frequently observed in tumor tissues (P = 0.001). The percentages of CD4 + Tm and CD8 + Tm were positively associated with DC1 percentage and ratio of DC1/DC2 (P < 0.05). The higher CD8 + Tcm percentage was associated with higher DC2 percentage (P = 0.025). The patients with high IDO expression had significantly lower CD4 + Tm (P = 0.012) and CD8 + Tm percentages (P = 0.033), but higher CD8 + Tem percentage (P < 0.01). Concerning on clinicopathologic features, the higher DC2 percentage was associated with larger tumor size (P = 0.019). The CD4 + Tm and CD8 + Tem percentages were significantly associated with clinical stage and lymph node metastasis; the high IDO expressions were significantly associated with deeper tumor invasion (P = 0.016) and lymph node metastasis (P = 0.038). Thus, DC subsets, Tm subsets, and IDO expression were correlated with each other. They were associated with the established clinicopathologic features, such as tumor size, depth of invasion, lymph node metastasis, and clinical stage.

We evaluated a clinical significance of indoleamine 2,3-dioxygenase (IDO) in thyroid cancers. Operative specimens obtained from 20 patients with thyroid cancers were investigated by semi-quantitative RT-PCR with specific primers against IDO. The correlations among IDO expression, clinicopathologic factors and prognosis were studied. An expression of IDO was observed in 100% for both of the cancer specimens and the non-cancer specimens. The IDO expression of cancer specimens was significantly higher than the non-cancer specimens. The expression of IDO did not correlate to histologic classification, tumor size, lymphatic invasion, venous invasion and lymph nodes metastasis, but it was correlated to clinical stage. There was no correlation for survival rate after surgery between the high IDO level group and low IDO level group. The serum IDO levels of cancer patients were higher than that of a healthy volunteer measured by semi-quantitative RT- PCR and HPLC. It is suggested that the expression of IDO in thyroid cancer patients may play critical role for immunosuppression of those patients.