title: IL4I1: an inhibitor of the CD8⁺ antitumor T-cell response in vivo.
abstract: 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-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.
authors.affiliation: INSERM, U955, Créteil, France.
authors.forename: Fanette
authors.initials: F
authors.lastname: Lasoudris
authors.forename: Céline
authors.initials: C
authors.lastname: Cousin
authors.forename: Armelle
authors.initials: A
authors.lastname: Prevost-Blondel
authors.forename: Nadine
authors.initials: N
authors.lastname: Martin-Garcia
authors.forename: Issam
authors.initials: I
authors.lastname: Abd-Alsamad
authors.forename: Nicolas
authors.initials: N
authors.lastname: Ortonne
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Farcet
authors.forename: Flavia
authors.initials: F
authors.lastname: Castellano
authors.forename: Valérie
authors.initials: V
authors.lastname: Molinier-Frenkel
mesh_terms: D000594:Amino Acid Oxidoreductases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D048708:Cell Growth Processes / Q000235:genetics / Q000276:immunology; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007114:Immunization; D007165:Immunosuppression Therapy; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000235:genetics; D008546:Melanoma, Experimental; D051379:Mice; D008822:Mice, Transgenic; D009374:Neoplasms, Experimental / Q000276:immunology*; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D019076:Transgenes / Q000235:genetics; D019139:Tumor Escape; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D000956:Antigens, Viral; D006023:Glycoproteins; D010446:Peptide Fragments; D014764:Viral Proteins; C094244:glycoprotein peptide 33-41, Lymphocytic choriomeningitis virus; D007371:Interferon-gamma; D006861:Hydrogen Peroxide; D000594:Amino Acid Oxidoreductases; C022342:phenylalanine oxidase