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Indoleamine 2,3-dioxygenase in tumor tissue indicates prognosis in patients with diffuse large B-cell lymphoma treated with R-CHOP

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Abstract

Indoleamine 2,3-dioxygenase (IDO) exerts immunomodulatory effects due to enzymatic activities catalyzing the essential amino acid l-tryptophan. IDO activity might play an important role in regulating immune responses exerted by antigen-presenting cells as a potent tool to help escape from assault by the immune system. In this study, we performed immunohistochemical analysis for IDO expression using mouse anti-human IDO monoclonal antibody in 119 tissue samples of diffuse large B-cell lymphoma (DLBCL) obtained before treatment with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Not only the lymphoma cells themselves but also dendritic cells (DCs) expressed IDO. Positive IDO expression in lymphoma cells was found in 38 cases (32%). Complete remission rates in patients with IDO-positive DLBCL and IDO-negative DLBCL were 55.3% and 79.0% (p = 0.008), while 3-year overall survival rates were 49.8% and 78.8%, respectively (p = 0.0003). IDO activity might thus play an important role in DLBCL and cells that express IDO appear important for determining outcomes after R-CHOP treatment. IDO might represent a candidate therapeutic target for DLBCL patients who show resistance to chemotherapy.

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Acknowledgement

The authors wish to thank Ms. Reiko Shinoda for her technical assistance.

Authorship

Contribution: S.N., M.H., and H.I. performed experiments; T.H., N.K., N.G., S.K., analyzed results and made the figures; K.S., Y.H., T.T., M.S., and T.T. contributed valuable tissues and clinical information; H.T., M.S. and H.M. designed the research and all authors contributed to writing and approved the paper.

Conflict of interest

The authors declare no competing financial interests.

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Authors and Affiliations

  1. First Department of Internal Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu, 501-1194, Japan

    Soranobu Ninomiya, Takeshi Hara, Hisashi Tsurumi, Nobuhiro Kanemura, Naoe Goto, Senji Kasahara, Masahito Shimizu & Hisataka Moriwaki

  2. Department of Informative Clinical Medicine, Gifu University Graduate School of Medicine, Gifu, Japan

    Masato Hoshi, Hiroyasu Ito & Mitsuru Seishima

  3. Department of Immunopathology, Gifu University Graduate School of Medicine, Gifu, Japan

    Naoe Goto & Tsuyoshi Takami

  4. Human Health Sciences, Graduate School of Medicine and Faculty of Medicine, Kyoto University, Kyoto, Japan

    Kuniaki Saito

  5. Department of Tumor Pathology, Gifu University Graduate School of Medicine, Gifu, Japan

    Yoshinobu Hirose

  6. Pathology, Gifu Municipal Hospital, Gifu, Japan

    Tetsuya Yamada

  7. Internal Medicine, Gifu Municipal Hospital, Gifu, Japan

    Takeshi Takahashi

Authors
  1. Soranobu Ninomiya
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  2. Takeshi Hara
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Corresponding author

Correspondence to Hisashi Tsurumi.

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Ninomiya, S., Hara, T., Tsurumi, H. et al. Indoleamine 2,3-dioxygenase in tumor tissue indicates prognosis in patients with diffuse large B-cell lymphoma treated with R-CHOP. Ann Hematol 90, 409–416 (2011). https://doi.org/10.1007/s00277-010-1093-z

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  • DOI: https://doi.org/10.1007/s00277-010-1093-z

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