The paradoxical patterns of expression of indoleamine 2,3-dioxygenase in colon cancer

Yan-Fang Gao,Ya Ding,Yi-Xin Zeng,Xiao-Jun Wu,Xing Zhang,Zhi-Zhong Pan,Rui-Qing Peng,Xiao-Shi Zhang,Jiang Li,De-Sen Wan

doi:10.1186/1479-5876-7-71

Abstract

BackgroundOne of the putative mechanisms of tumor immune escape is based on the hypothesis that carcinomas actively create an immunosuppressed state via the expression of indoleamine 2,3-dioxygenase (IDO), both in the cancer cells and in the immune cells among the tumor-draining lymph nodes (TDLN). In an attempt to verify this hypothesis, the patterns of expression of IDO in the cancer cells and the immune cells among colon cancers were examined.MethodsSeventy-one cases of pathologically-confirmed colon cancer tissues matched with adjacent non-cancerous tissues, lymph node metastases, and TDLN without metastases were collected at the Sun Yat-sen Cancer Center between January 2000 and December 2000. The expression of IDO and Bin1, an IDO regulator, was determined with an immunohistochemical assay. The association between IDO or Bin1 expression and TNM stages and the 5-year survival rate in colon cancer patients was analyzed.ResultsIDO and Bin1 were detected in the cytoplasm of cancer cells and normal epithelium. In primary colon cancer, the strong expression of IDO existed in 9/71 cases (12.7%), while the strong expression of Bin1 existed in 33/71 cases (46.5%). However, similar staining of IDO and Bin1 existed in the adjacent non-cancerous tissues. Among the 41 cases with primary colon tumor and lymph node metastases, decreased expression of IDO was documented in the lymph node metastases. Furthermore, among the TDLN without metastases, a higher density of IDO+cells was documented in 21/60 cases (35%). Both univariate and multivariate analyses revealed that the density of IDO+cells in TDLN was an independent prognostic factor. The patients with a higher density of IDO+cells in TDLN had a lower 5-year survival rate (37.5%) than the cells with a lower density (73.1%).ConclusionThis study demonstrated paradoxical patterns of expression of IDO in colon cancer. The high density IDO+cells existed in TDLN and IDO was down-regulated in lymph nodes with metastases, implying that IDO in tumor and immune cells functions differently.

Highlights

One of the putative mechanisms of tumor immune escape is based on the hypothesis that carcinomas actively create an immunosuppressed state via the expression of indoleamine 2,3-dioxygenase (IDO), both in the cancer cells and in the immune cells among the tumor-draining lymph nodes (TDLN)
The results showed the paradoxical patterns of expression of IDO; both a higher density of IDO+cells in TDLN and down-regulation of IDO in metastatic cancer cells were associated with poor prognosis in colon cancers
The expression of IDO was detected on dendritic cell-like cells in the TDLN without metastases, which were derived from 27 patients without lymph node involvement (N0) and 33 patients with lymph node involvement (N1–3; Fig. 1D)

Summary

Introduction

One of the putative mechanisms of tumor immune escape is based on the hypothesis that carcinomas actively create an immunosuppressed state via the expression of indoleamine 2,3-dioxygenase (IDO), both in the cancer cells and in the immune cells among the tumor-draining lymph nodes (TDLN). Animal tumors expressing a higher level of IDO effectively escape from immune surveillance of the host by degrading local tryptophan, which in turn inhibits T cell responses [10,11]. It is widely thought that either or both of these sites of IDO expression serve to inhibit immune responses to tumors, the supporting evidence is insufficient [22,23,24,25]

Methods

Results

Discussion

Conclusion