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:10.1371/journal.pone.0078730

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

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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.

Original language	English
Article number	e78730
Journal	PloS one
Volume	8
Issue number	11
DOIs	https://doi.org/10.1371/journal.pone.0078730
Publication status	Published - 13-11-2013
Externally published	Yes

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10.1371/journal.pone.0078730

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title = "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.",

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

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doi = "10.1371/journal.pone.0078730",

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T1 - Clinical significance of sIL-2R levels in B-cell lymphomas

AU - Yoshida, Noriaki

AU - Oda, Miyo

AU - Kuroda, Yoshiaki

AU - Katayama, Yuta

AU - Okikawa, Yoshiko

AU - Masunari, Taro

AU - Fujiwara, Megumu

AU - Nishisaka, Takashi

AU - Sasaki, Naomi

AU - Sadahira, Yoshito

AU - Mihara, Keichiro

AU - Asaoku, Hideki

AU - Matsui, Hirotaka

AU - Seto, Masao

AU - Kimura, Akiro

AU - Arihiro, Koji

AU - Sakai, Akira

PY - 2013/11/13

Y1 - 2013/11/13

N2 - 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.

AB - 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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JO - PloS one

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IS - 11

M1 - e78730

ER -

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

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