Clinical Significance of sIL-2R Levels in B-Cell Lymphomas

Abstract

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.

A rare CD5-positive subgroup of diffuse large B-cell lymphoma – clinical, morphological and immunophenotypic features in Polish patients

“…The majority of authors have reported similar observations to those made in the present study, namely that the expression of MMPs in malignant cells, including MMP-9, is associated with unfavorable prognosis in patients with aggressive NHL, such as DLBCL [49,50,51]. Feng et al reported that the expression of MMP-9 was higher in DLBCL in clinical stage III and IV in comparison to clinical stage I and II [52].…”

Acute Myeloid Leukemia Concurrent with Spinal Epidural Extramedullary Myeloid Sarcoma Accompanied by a High CD25 Expression and the <i>FLT3-ITD</i> Mutation

“…In the setting of malignant lymphoma, no distinct correlations between the CD25 expression on B-lymphoma cells and the sIL-2R level have been observed, and most CD25-expressing cells in the tumors are T-cells (19). In the present case, the mechanism underlying the extremely elevated serum sIL-2R levels differed from that of malignant lymphoma; however, a high CD25 expression in leukemic cells may result in an extremely elevated sIL-2R level, which makes it difficult to distinguish MS from malignant lymphoma.…”

The emerging role of anti‐CD25 directed therapies as both immune modulators and targeted agents in cancer

“…Both (HL) and non-Hodgkin lymphoma (NHL) malignant cells have demonstrated expression of CD25 (Tesch et al, 1993;Waldmann, 2007). NHL tumours with high levels of surface CD25 expression include DLBCL (Hashimoto et al, 2013;Yoshida et al, 2013), follicular lymphoma (Yoshida et al, 2013) and peripheral T cell lymphoma including angioimmunoblastic T cell lymphoma and anaplastic large cell lymphoma (Gualco et al, 2009). Rarer diseases showing CD25 expression include Waldenstr€ om macroglobuliaemia (San Miguel et al, 2003) and systemic mastocytosis, which is defined by its CD25 expression (Lim et al, 2009).…”