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
中科院分区:
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
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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