细胞因子环境中淋巴瘤基质细胞壁龛功能性改变之——吲哚胺2，3加双氧酶的作用

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主题：细胞因子环境中淋巴瘤基质细胞壁龛功能性改变之——吲哚胺2，3加双氧酶的作用
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说明：原文来自Cancer Research，干细胞之家新闻小组成员deron翻译（转帖请注明）% ?; n. v4 l: b6 f: X  P

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2 k# e3 |* k" T细胞因子环境中淋巴瘤基质细胞壁龛功能性改变之——吲哚胺2，3加双氧酶的作用
2 K9 t: F, i- ]  P& k" J人间充质干细胞（MSC）可以通过生成一系列复杂可溶性因子（包括由IFN-γ 诱导的色氨酸异化酶IDO），强力抑制活化T细胞的增殖。相反地，MSCs，尤其在经过肿瘤坏死因子α（TNFα）和淋巴毒素α1β2（LTα1β2）刺激之后，可以维持滤泡性淋巴瘤（FL）B细胞的生存。在稳态和炎性环境下，MSCs对正常和恶化B细胞生长过程发挥的作用有待全面探究。本文中我们证明了静态MSCs支持正常活化B细胞增殖和生存，然而IFN-γ环境下，MSCs诱导IDO依赖的B细胞生长停滞和凋亡。在FL淋巴瘤浸润的微环境中，IFN-γ，TNF和LT表达显著上调，但是不同样本中它们各自的表达方式呈现多样化。在体外，IFN-γ可以消除MSC表面由TNF和LT诱导的B细胞支持表型。此外，IFN-γ能够抑制MSC对纯化FL B细胞的生长促进作用。总之，这些结果突出了细胞因子环境在恶性细胞及其微环境局部相互作用中的重要性，并为FL细胞壁龛理解融入了新的认识，这一进展可以为治疗方案的改革创新提供新的方向。
/ a: W+ Q; ]4 j5 F  o  P! |原摘要：Human mesenchymal stem cells (MSC) strongly repress activated T-cell proliferation through the production of a complex set of soluble factors, including the tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase (IDO), which is induced by IFN-gamma. Conversely, MSCs support survival of follicular lymphoma (FL) B cells, in particular after exposure to tumor necrosis factor-alpha (TNF) and lymphotoxin-alpha1beta2 (LT). The role of MSCs on normal and malignant B-cell growth in steady-state and inflammatory conditions remains to be fully explored. We show here that resting MSCs sustain activated normal B-cell proliferation and survival, whereas IFN-gamma-conditioned MSCs mediate IDO-dependent B-cell growth arrest and apoptosis. IFN-gamma, TNF, and LT are significantly overexpressed by the microenvironment of invaded FL-lymph nodes, but their relative expression patterns are highly heterogeneous between samples. In vitro, IFN-gamma abrogates the B-cell supportive phenotype induced by TNF and LT on MSCs. Moreover, IFN-gamma overrules the growth promoting effect of MSCs on primary purified FL B cells. Altogether, these results underline the crucial role of the cytokine context in the local crosstalk between malignant cells and their microenvironment and provide new insights into our knowledge of the FL cell niche that emerges as a new promising target for innovative therapeutic strategies./ m/ s* R# ?$ ~" m/ C# e* @
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