Clinical significance of sIL-2R levels in B-cell lymphomas.
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.
Department of Hematology and Oncology, Research Institute Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan ; Division of Molecular Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan ; Department of Cancer Genetics, Nagoya University Graduate School of Medicine at Aichi Cancer Center Research Institute, Nagoya, Japan.
Noriaki
N
Yoshida
Miyo
M
Oda
Yoshiaki
Y
Kuroda
Yuta
Y
Katayama
Yoshiko
Y
Okikawa
Taro
T
Masunari
Megumu
M
Fujiwara
Takashi
T
Nishisaka
Naomi
N
Sasaki
Yoshito
Y
Sadahira
Keichiro
K
Mihara
Hideki
H
Asaoku
Hirotaka
H
Matsui
Masao
M
Seto
Akiro
A
Kimura
Koji
K
Arihiro
Akira
A
Sakai
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000097:blood*; D045744:Cell Line, Tumor; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D016393:Lymphoma, B-Cell / Q000097:blood* / Q000401:mortality / Q000473:pathology; D008264:Macrophages / Q000201:enzymology; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D011379:Prognosis; D011956:Receptors, Cell Surface / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000097:blood*; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D059016:Tumor Microenvironment; D000098902:CD163 Antigen; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D014408:Biomarkers, Tumor; D053645:Interleukin-2 Receptor alpha Subunit; D020780:Matrix Metalloproteinase 9; D011956:Receptors, Cell Surface; D015375:Receptors, Interleukin-2; D000098902:CD163 Antigen; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C508017:IL2RA protein, human; C579270:MMP9 protein, human