Clinical significance of sIL-2R levels in B-cell lymphomas.

Clinical significance of sIL-2R levels in B-cell lymphomas.
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DOI:
10.1371/journal.pone.0078730
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Sakai A
Sakai A
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Yoshida N;Oda M;Kuroda Y;Katayama Y;Okikawa Y;Masunari T;Fujiwara M;Nishisaka T;Sasaki N;Sadahira Y;Mihara K;Asaoku H;Matsui H;Seto M;Kimura A;Arihiro K;Sakai A

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在恶性淋巴瘤 (ML) 患者中观察到血清中可溶性白细胞介素 2 受体 (sIL-2R) 升高。因此,sIL-2R 通常用作 ML 的诊断和预后标志物,但 B 细胞淋巴瘤患者中 sIL-2R 水平升高的机制尚未阐明。我们首先假设肿瘤微环境中表达IL-2R和一些蛋白酶(例如基质金属蛋白酶(MMP))的淋巴瘤细胞可以引起血清中sIL-2R的增加。然而,流式细胞术研究显示,在弥漫性大B细胞淋巴瘤(DLBCL)和滤泡性淋巴瘤(FL)中,很少有淋巴瘤细胞表达IL-2Rα链(CD25),并且肿瘤中大多数表达CD25的细胞是T细胞。未观察到 B 淋巴瘤细胞上的 CD25 表达与 sIL-2R 水平之间的明显相关性。然后我们证实MMP-9在功能研究中在产生sIL-2R中发挥重要作用。免疫组织化学 (IHC) 分析还表明,MMP-9 主要来源于肿瘤相关巨噬细胞 (TAM)。因此,我们使用 IHC 分析评估了肿瘤微环境中 CD68 和 CD163 阳性巨噬细胞的数量。在 FL 和结外 DLBCL 中证实血清中 sIL-2R 水平与肿瘤微环境中 CD68 阳性巨噬细胞数量呈正相关。这些结果可能有助于了解 B 细胞淋巴瘤的病理生理学。
Elevated soluble interleukin-2 receptor (sIL-2R) in sera is observed in patients with malignant lymphoma (ML). Therefore, sIL-2R is commonly used as a diagnostic and prognostic marker for ML, but the mechanisms responsible for the increase in sIL-2R levels in patients with B-cell lymphomas have not yet been elucidated. We first hypothesized that lymphoma cells expressing IL-2R and some proteinases such as matrix metalloproteinases (MMPs) in the tumor microenvironment can give rise to increased sIL-2R in sera. However, flow cytometric studies revealed that few lymphoma cells expressed IL-2R α chain (CD25) in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL), and most CD25-expressing cells in the tumor were T-cells. Distinct correlations between CD25 expression on B-lymphoma cells and sIL-2R levels were not observed. We then confirmed that MMP-9 plays an important role in producing sIL-2R in functional studies. Immunohistochemical (IHC) analysis also revealed that MMP-9 is mainly derived from tumor-associated macrophages (TAMs). We therefore evaluated the number of CD68 and CD163 positive macrophages in the tumor microenvironment using IHC analysis. A positive correlation between the levels of sIL-2R in sera and the numbers of CD68 positive macrophages in the tumor microenvironment was confirmed in FL and extranodal DLBCL. These results may be useful in understanding the pathophysiology of B-cell lymphomas.
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