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

Our plain-English summary of IL4I1: an inhibitor of the CD8⁺ antitumor T-cell response in vivo, by F. Lasoudris, C. Cousin, A. Prevost-Blondel, et al (European Journal of Immunology, 2011).

The study

• Authors: F. Lasoudris, C. Cousin, A. Prevost-Blondel, N. Martin-Garcia, I. Abd-Alsamad, N. Ortonne, J.P. Farcet, F. Castellano, V. Molinier-Frenkel
• Journal: European Journal of Immunology
• Published: 2011;41(6):1629-38
• Cited by: 65 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

In plain English

This was a laboratory study in mice, with a small set of human tumor samples. It did not study asbestos exposure. The authors, working in France, tested whether IL4I1, an enzyme that can suppress immune T cells, helps tumors escape the immune system. They engineered mouse melanoma cells to produce IL4I1 and injected them into mice that had been vaccinated against a marker carried by the tumor cells. Mice given control cells were fully protected, while more than 50% of mice given IL4I1-producing cells developed tumors. When only 20% of the injected cells produced IL4I1, 25% of mice developed tumors, compared with 4% of control mice. Mice with IL4I1-producing tumors had fewer tumor-targeting CD8 T cells, and those cells made less interferon-gamma. The authors also measured IL4I1 activity in four human melanomas and seven human mesotheliomas. Activity was high in all but one mesothelioma. The authors concluded that IL4I1 severely compromises anti-tumor immune functions in this model and may contribute to the progression of human tumors.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Animal experiment: a mouse melanoma tumor model engineered to express the enzyme IL4I1, plus enzyme-activity measurements in a small number of human tumor samples
• Who was studied: C57BL/6 mice, 6 to 10 weeks old, in groups of 10 or 14 per experiment for the main tumor-growth tests. Also four human melanoma biopsies with matching normal skin, and seven human mesotheliomas. Research done in France.
• Exposure: No asbestos exposure was studied. The experimental factor was IL4I1 enzyme production by B16GP33 mouse melanoma cells. Two IL4I1-producing clones (B8 and B11) were compared with a control clone (A1) that carried an empty vector.
• Main results:
  • In mice vaccinated 7 days before tumor challenge, all mice given control A1 cells were protected. More than 50% of mice given the IL4I1-producing clones developed tumors (p = 0.012 for B8 versus A1; p = 0.004 for B11 versus A1).
  • When tumor cells were injected 28 days after vaccination, 77% of A1-challenged mice controlled tumors at day 80. More than 70% of B8- and B11-challenged mice developed a melanoma (p = 0.049).
  • Tumors developed in 4% of control mice receiving 100% A1 cells and in 68% of mice receiving 100% B11 cells. With at least 20% B11 cells, tumors developed in 25% of mice, which was significantly higher than in controls.
  • Tumor-specific CD8 T cells in the spleen averaged 6.2% in A1-challenged mice, versus 3.1% in B8-challenged mice and 2.6% in B11-challenged mice.
  • The interferon-gamma response against the tumor marker fell by 53% in spleen cells from B8-challenged mice and by 84% in spleen cells from B11-challenged mice, compared with A1-challenged mice.
  • Killing of target cells was lower in B11-challenged mice than in control mice. The difference averaged 15% and was significant from day 3 to day 8.
  • In the four human melanomas, IL4I1 activity ranged from 15 to 29 activity units. This was significantly different from the negligible activity in normal skin.
  • IL4I1 activity was high in all but one of the seven human mesotheliomas (mean 98; range 16 to 261 activity units).
• The authors' conclusion: The authors concluded that IL4I1 severely compromises anti-tumor functions of the host immune system and may contribute to the progression of human tumors. They suggested that IL4I1 inhibitors be evaluated as a way to improve antitumor immunotherapies.

Topics

Medical terms in this study, explained in our Lexicon: Macrophage, Immunohistochemistry, Mesothelioma.

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