The Research On Function Of Indoleamine2,3-dioxygenase And Regulatory T Cells Participating In The Progression And Metastasis Of Colon Carcinoma

Objective:To detect the expression differences of indoleamine2,3-dioxygenase (IDO) and forkhead/winged helix transcription factor (Foxp3), which is the landmark molecules of regulatory T cells (Tregs), in primary tumor of colon carcinoma, adjacent normal colon tissue and tumor draining lymph nodes (TDLNs), then to seek the relationship between IDO and Foxp3, evaluating the relationship between above mentioned proteins and various clinical-pathological characteristics. The effect of IDO and Tregs was explored in tumorigenesis and metastasis of colon carcinoma.Methods:The paraffin blocks and fresh tissues of58cases of colon carcinomas including primary tumor, adjacent normal colon tissue and TDLNs, which were explicit diag-nosed by pathology department. were collected from Tianjin Medical University General hospital in January2011to November2011. Immunohistoche-mistry was used to detect the expression of IDO and Foxp3proteins in previous tissues. To analyze the clinical pathological data for all patients, then to seek the relationship between them.Results:1. The expression of IDO and Foxp3in colon carcinomas IDO was mostly located in cytoplasm; Foxp3was mostly located in nucleus. IDO was expressed with different staining intensity in primary tumor, adjacent normal tissue and TDLNs.2. The differential expression of IDO and Foxp3in different tissues of colon carcinomas(1) IDO was over-expressed in primary tumor of human colon carcinomas. Im-munohistochemistry results showed that IDO positive expression rate and cell index were98.3%(57/58) and (22.3±8.22)%. The expression level of IDO in primary tumor was higher than adjacent normal tissue[65.5%(38/58),(11.72±3.49)%](P<0.05).24of58tumor specimens had TDLNs metastasis, in which the expressing was different staining intensity. By contrast, in24TDLNs metastasis, IDO was obviously down regulation comparing to24primary tumors(P<0.05).(2) The percentage of Foxp3+cells in primary tumor[(3.51±2.80)%] was higher than adjacent normal tissue [(1.29±0.99)%](P<0.05). The TDLNs[(7.53±4.68)%] was higher than primary tumor and adjacent normal tissue (P<0.05).3. The relationship among IDO, Foxp3and clinical-pathological characteristics of the patientsSignificant association of IDO expression in primary tumor tissues with lymph node metastasis and TNM staging (P<0.05) were found; Significant association of Foxp3expression in primary tumor tissues with lymph node metastasis (P<0.05) were found. Spearman rank correlation showed that IDO correlates positively with Foxp3significantly with regard to positive expression rate (rs=0.331, P=0.011).Conclusion:1. IDO was over-expressed in primary tumor tissues with lymph node metastasis, which implied IDO might have a role in tumor immune escape; In the metastatic process of colon carcinomas cells towards tumor draining lymph nodes, IDO was down regulation in TDLNs metastasis, but Foxp3was over-ex-pressed. The results hinted that the progression and metastasis of tumor were not by catalyzing tryptophan metabolism locally in TDLNs metastasis, but by Tregs which played a role in immunosuppression.2. The positive expression of IDO was significant higher in metastasis of draining lymph node and worse TNM staging than those in no-metastasis of draining lymph node and better TNM staging in colon cancer, which implied the upregulation of IDO expression in colon carcinoma was correlated to grade malignancy. IDO may be an indicator of colon carcinoma prognosis.3. IDO correlates positively with Tregs significantly, suggesting that IDO might be interaction with Tregs, contributing to progress and metastasis of colon carcinoma and participating in colon carcinoma immune escape by inducing differentiation of Tregs possibly.