PLoS ONE (Jan 2013)

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

  • Noriaki Yoshida,
  • Miyo Oda,
  • Yoshiaki Kuroda,
  • Yuta Katayama,
  • Yoshiko Okikawa,
  • Taro Masunari,
  • Megumu Fujiwara,
  • Takashi Nishisaka,
  • Naomi Sasaki,
  • Yoshito Sadahira,
  • Keichiro Mihara,
  • Hideki Asaoku,
  • Hirotaka Matsui,
  • Masao Seto,
  • Akiro Kimura,
  • Koji Arihiro,
  • Akira Sakai

DOI
https://doi.org/10.1371/journal.pone.0078730
Journal volume & issue
Vol. 8, no. 11
p. e78730

Abstract

Read online

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.