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Lymphoma

The novel immunosuppressive enzyme IL4I1 is expressed by neoplastic cells of several B-cell lymphomas and by tumor-associated macrophages

Leukemia volume 23, pages 952–960 (2009)Cite this article

Abstract

We previously reported a strong IL4I1 gene expression in primary mediastinal B-cell lymphoma (PMBL) and recently identified the protein as a secreted L-phenylalanine oxidase, physiologically expressed by myeloid cells, which inhibits T-cell proliferation in vitro. Here, we analyzed the pattern of IL4I1 protein expression in 315 human lymphoid and non-lymphoid malignancies. Besides PMBL, IL4I1 expression in tumors was very frequent. IL4I1 was detected in tumor-associated macrophages from most of the tumors and in neoplastic cells from follicular lymphoma, classic and nodular lymphocyte predominant Hodgkin lymphomas and small lymphocytic lymphoma, three of which are germinal center derived. IL4I1-positive tumor cells were also detected in rare cases of solid cancers, mainly mesothelioma. The enzymatic activity paralleled protein expression, suggesting that IL4I1 is functional in vivo. Depending on the tumor type, IL4I1 may impact on different infiltrating lymphocyte populations with consequences on tumor evolution. In the particular case of follicular lymphoma cells, which are susceptible to antitumor cytotoxic T cells killing but depend on interactions with local T helper cells for survival, a high level of IL4I1 expression seems associated with the absence of bone marrow involvement and a better outcome. These findings plead for an evaluation of IL4I1 as a prognosis factor.

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Acknowledgements

This work was supported by ARC subvention fixe 4883 to FC. We are indebted to Willam Hempel for critical reading and English editing of the article. We thank the Plateforme de ressources biologiques of Henri Mondor Hospital, Dr Françoise Lange, Dr Jeanne Tran Van Nhieu and Dr Annabelle Werbrouck for providing precious human samples. We are also grateful to Jeanine Marquet, Rita Colognon, Céline Cousin, Antoine Allain and Marie-Claude Bassène for technical assistance and to all the clinicians from the Unité Hémopathies Lymphoïdes of CHU Mondor-Chenevier. We are indebted to the association for therapeutic, genetic and immunologic research on lymphoma (ARTGIL) for providing financial support to MB.

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Authors and Affiliations

  1. Faculté de Médecine, Université Paris 12, Créteil, France

    A Carbonnelle-Puscian, C Copie-Bergman, M Baia, N Martin-Garcia, Y Allory, J-P Farcet, P Gaulard, F Castellano & V Molinier-Frenkel

  2. Département de Pathologie, AP-HP, Groupe hospitalier Henri Mondor-Albert Chenevier, Créteil, France

    A Carbonnelle-Puscian, C Copie-Bergman, M Baia, Y Allory & P Gaulard

  3. INSERM, Unité 955, IMRB, Créteil, France

    C Copie-Bergman, M Baia, N Martin-Garcia, A Crémades, J-P Farcet, P Gaulard, F Castellano & V Molinier-Frenkel

  4. Unité Hémopathies Lymphoïdes, AP-HP, Groupe hospitalier Henri Mondor-Albert Chenevier, Créteil, France

    C Haioun

  5. Centre Hospitalier Intercommunal de Créteil, Service d'Anatomie et Cytologie Pathologique, Créteil, France

    I Abd-Alsamad

  6. Service d'Immunologie Biologique, AP-HP, Groupe hospitalier Henri Mondor-Albert Chenevier, Créteil, France

    J-P Farcet, F Castellano & V Molinier-Frenkel

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  1. A Carbonnelle-Puscian
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Correspondence to F Castellano or V Molinier-Frenkel.

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Carbonnelle-Puscian, A., Copie-Bergman, C., Baia, M. et al. The novel immunosuppressive enzyme IL4I1 is expressed by neoplastic cells of several B-cell lymphomas and by tumor-associated macrophages. Leukemia 23, 952–960 (2009). https://doi.org/10.1038/leu.2008.380

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