IL4I1: an inhibitor of the CD8+ antitumor T‐cell response in vivo
Open Access
- 21 March 2011
- journal article
- research article
- Published by Wiley in European Journal of Immunology
- Vol. 41 (6), 1629-1638
- https://doi.org/10.1002/eji.201041119
Abstract
The L‐phenylalanine oxidase IL4I1 inhibits T‐cell proliferation in vitro through H2O2 production, and is highly expressed in tumor‐associated macrophages. IL4I1 is also detected by immunohistochemistry in neoplastic cells from several B‐cell lymphomas and some non‐lymphoid tumors. To evaluate IL4I1's effect on tumor growth, we developed a mouse melanoma model constitutively coexpressing IL4I1 and the GP33 epitope. After GP33 vaccination, tumors developed more frequently in mice injected with IL4I1‐expressing cells in comparison with mice receiving control cells. Tumor escape was preceded by a rapid diminution of IFN‐γ‐producing cytotoxic antitumor CD8+ T cells. Moreover, tumor incidence was already increased when only 20% of the injected cells expressed IL4I1. The minimal IL4I1 activities leading to tumor escape were close to those detected in human melanoma and mesothelioma. Thus, we demonstrate the immunosuppressive functions of IL4I1 in vivo and suggest that IL4I1 facilitates human tumor growth by inhibiting the CD8+ antitumor T‐cell response.Keywords
This publication has 28 references indexed in Scilit:
- The biology of myeloid‐derived suppressor cells: The blessing and the curse of morphological and functional heterogeneityEuropean Journal of Immunology, 2010
- Dichotomy between factors inducing the immunosuppressive enzyme IL‐4‐induced gene 1 (IL4I1) in B lymphocytes and mononuclear phagocytesEuropean Journal of Immunology, 2010
- Alternative Activation of Macrophages: Mechanism and FunctionsImmunity, 2010
- Expression and prognostic significance of iNOS in uveal melanomaInternational Journal of Cancer, 2010
- Arginase: an emerging key player in the mammalian immune systemBritish Journal of Pharmacology, 2009
- Myeloid-derived suppressor cells as regulators of the immune systemNature Reviews Immunology, 2009
- The novel immunosuppressive enzyme IL4I1 is expressed by neoplastic cells of several B-cell lymphomas and by tumor-associated macrophagesLeukemia, 2009
- Prognostic significance of tumor iNOS and COX-2 in stage III malignant cutaneous melanomaCancer Immunology, Immunotherapy, 2008
- Tumor‐induced tolerance and immune suppression by myeloid derived suppressor cellsImmunological Reviews, 2008
- Indoleamine 2,3-dioxygenase and tumor-induced toleranceJCI Insight, 2007