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Open Access Research article

Indoleamine 2,3-dioxygenase (IDO) is frequently expressed in stromal cells of Hodgkin lymphoma and is associated with adverse clinical features: a retrospective cohort study

Ji-Young Choe1, Ji Yun Yun1, Yoon Kyoung Jeon2, Se Hoon Kim3, Gyeongsin Park4, Joo Ryoung Huh5, Sohee Oh6 and Ji Eun Kim7*

Author Affiliations

1 Department of Pathology, Seoul National University Bundang Hospital, Seongnam-si, Korea

2 Department of Pathology, Seoul National University Hospital, Seoul, Korea

3 Department of Pathology, Yonsei University College of Medicine, Seoul, Korea

4 Department of Pathology, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, Korea

5 Department of Pathology, Asan Medical Center, Seoul, Korea

6 Department of Biostatistics, Seoul National University Boramae Hospital, Seoul, Korea

7 Department of Pathology, Seoul National University Boramae Hospital, Seoul, Korea

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BMC Cancer 2014, 14:335  doi:10.1186/1471-2407-14-335

Published: 15 May 2014

Abstract

Background

Regulation of tumor microenvironment is closely involved in the prognosis of Hodgkin lymphoma (HL). Indoleamine 2,3-dioxygenase (IDO) is an enzyme acting as immune modulator through suppression of T-cell immunity. This study aims to investigate role of IDO in the microenvironment of HL.

Methods

A total of 121 cases of HL were enrolled to do immunohistochemistry for IDO, CD163, CD68, CD4, CD8, and FoxP3. Positivity was evaluated from area fractions or numbers of positive cells using automated image analyzer. Correlations between IDO expression and various cellular infiltrates and clinicopathologic parameters were examined and survival analyses were performed.

Results

IDO was expressed in histiocytes, dendritic cells and some endothelial cells with variable degrees, but not in tumor cells. IDO positive cells were more frequently found in mixed cellularity type than other histologic types, and in cases with EBV+, high Ann Arbor stages, B symptoms, and high IPS (all p < 0.05). High IDO expression was associated with inferior survival (p < 0.001) and reflects an independent prognostic factor in nodular sclerosis HL.

Conclusions

This is the first study suggesting that IDO is the principle immunomodulator and is involved to adverse clinical outcomes of HL.

Keywords:
Hodgkin disease; Indoleamine-pyrrole 2,3-dioxygenase; Macrophages; Stromal cells; Tumor microenvironment; Epstein-barr virus infections; Pathology