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Publication : IL4I1: an inhibitor of the CD8⁺ antitumor T-cell response in vivo.

First Author  Lasoudris F Year  2011
Journal  Eur J Immunol Volume  41
Issue  6 Pages  1629-38
PubMed ID  21469114 Mgi Jnum  J:302454
Mgi Id  MGI:6508501 Doi  10.1002/eji.201041119
Citation  Lasoudris F, et al. (2011) IL4I1: an inhibitor of the CD8(+) antitumor T-cell response in vivo. Eur J Immunol 41(6):1629-38
abstractText  The L-phenylalanine oxidase IL4I1 inhibits T-cell proliferation in vitro through H(2) O(2) 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-gamma-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.
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