IL4I1: an inhibitor of the CD8+ antitumor T-cell response in vivo
IL4I1: an inhibitor of the CD8+ antitumor T-cell response in vivo
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DOI：
10.1002/eji.201041119
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发表时间：
2011-06-01
影响因子：
5.4
通讯作者：
Molinier-Frenkel, Valerie
中科院分区：
文献类型：
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作者：
Lasoudris, Fanette;Cousin, Celine;Molinier-Frenkel, Valerie
l -苯丙氨酸氧化酶IL4I1通过产生H2O2抑制体外t细胞增殖，并在肿瘤相关巨噬细胞中高表达。免疫组化也可在几种b细胞淋巴瘤和一些非淋巴样肿瘤的肿瘤细胞中检测到IL4I1。为了评估IL4I1对肿瘤生长的影响，我们建立了一个组成型共表达IL4I1和GP33表位的小鼠黑色素瘤模型。GP33疫苗接种后，与接受对照细胞的小鼠相比，注射表达il4i1细胞的小鼠肿瘤发生频率更高。肿瘤逃逸之前，产生ifn - γ的细胞毒性抗肿瘤CD8(+) T细胞迅速减少。此外，当只有20%的注射细胞表达IL4I1时，肿瘤发病率已经增加。导致肿瘤逃逸的最小IL4I1活性接近于在人类黑色素瘤和间皮瘤中检测到的活性。因此，我们在体内证明了IL4I1的免疫抑制功能，并表明IL4I1通过抑制CD8（+）抗肿瘤t细胞反应促进人类肿瘤生长。
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-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.