The novel immunosuppressive enzyme IL4I1 is expressed by neoplastic cells of several B-cell lymphomas and by tumor-associated macrophages
The novel immunosuppressive enzyme IL4I1 is expressed by neoplastic cells of several B-cell lymphomas and by tumor-associated macrophages
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DOI：
10.1038/leu.2008.380
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发表时间：
2009-05-01
期刊：
影响因子：
11.4
通讯作者：
Molinier-Frenkel, V.
中科院分区：
文献类型：
--
作者：
Carbonnelle-Puscian, A.;Copie-Bergman, C.;Molinier-Frenkel, V.
我们之前报道了原发性纵隔b细胞淋巴瘤（PMBL）中IL4I1基因的强表达，最近发现该蛋白是一种分泌的l -苯丙氨酸氧化酶，由髓细胞生理表达，在体外抑制t细胞增殖。在这里，我们分析了IL4I1蛋白在315人淋巴样和非淋巴样恶性肿瘤中的表达模式。除PMBL外，IL4I1在肿瘤中的表达也非常频繁。IL4I1在大多数肿瘤的肿瘤相关巨噬细胞中检测到，在滤泡性淋巴瘤、典型和结节淋巴细胞为主的霍奇金淋巴瘤和小淋巴细胞淋巴瘤的肿瘤细胞中检测到，其中三种是生发中心来源的。在罕见的实体癌（主要是间皮瘤）中也检测到il4i1阳性的肿瘤细胞。酶活性与蛋白表达平行，表明IL4I1在体内具有功能。根据肿瘤类型的不同，IL4I1可能影响不同的浸润淋巴细胞群，从而影响肿瘤的进化。在滤泡性淋巴瘤细胞的特殊情况下，滤泡性淋巴瘤细胞易受抗肿瘤细胞毒性T细胞的杀伤，但依赖于与局部T辅助细胞的相互作用来生存，IL4I1的高水平表达似乎与不累及骨髓和更好的结果有关。这些发现为IL4I1作为预后因素的评估提供了依据。白血病（2009）23,952 -960；doi: 10.1038 / leu.2008.380;2009年1月29日在线发布
We previously reported a strong IL4I1 gene expression in primary mediastinal B-cell lymphoma (PMBL) and recently identified the protein as a secreted L-phenylalanine oxidase, physiologically expressed by myeloid cells, which inhibits T-cell proliferation in vitro. Here, we analyzed the pattern of IL4I1 protein expression in 315 human lymphoid and non-lymphoid malignancies. Besides PMBL, IL4I1 expression in tumors was very frequent. IL4I1 was detected in tumor-associated macrophages from most of the tumors and in neoplastic cells from follicular lymphoma, classic and nodular lymphocyte predominant Hodgkin lymphomas and small lymphocytic lymphoma, three of which are germinal center derived. IL4I1-positive tumor cells were also detected in rare cases of solid cancers, mainly mesothelioma. The enzymatic activity paralleled protein expression, suggesting that IL4I1 is functional in vivo. Depending on the tumor type, IL4I1 may impact on different infiltrating lymphocyte populations with consequences on tumor evolution. In the particular case of follicular lymphoma cells, which are susceptible to antitumor cytotoxic T cells killing but depend on interactions with local T helper cells for survival, a high level of IL4I1 expression seems associated with the absence of bone marrow involvement and a better outcome. These findings plead for an evaluation of IL4I1 as a prognosis factor. Leukemia (2009) 23, 952-960; doi:10.1038/leu.2008.380; published online 29 January 2009