IL-10 induces the development of immunosuppressive CD14+ HLA-DRlow/- monocytes in B-cell non-Hodgkin lymphoma

B. Xiu, Yi Lin, D. M. Grote, S. C. Ziesmer, Michael Gustafson, M. L. Maas, Z. Zhang, Allan B Dietz, L. F. Porrata, Anne J Novak, A. B. Liang, Z. Z. Yang, Stephen Maxted Ansell

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

The biological role of monocytes and macrophages in B-cell non-Hodgkin lymphoma (NHL) is not fully understood. We have previously reported that monocytes from patients with B-cell NHL have an immunosuppressive CD14+HLA-DRlow/- phenotype that correlates with a poor prognosis. However, the underlying mechanism by which CD14+HLA-DRlow/- monocytes develop in lymphoma is unknown. In the present study, we found that interleukin (IL)-10, which is increased in the serum of patients with B-cell NHL, induced the development of the CD4+HLA-DRlow/- population. Using peripheral blood samples from patients with B-cell NHL, we found that absolute numbers of CD14+ monocytic cells with an HLA-DRlow/- phenotype were higher than healthy controls and correlated with a higher International Prognostic Index score. IL-10 serum levels were elevated in lymphoma patients compared with controls and were associated with increased peripheral monocyte counts. Treatment of monocytes with IL-10 in vitro significantly decreased HLA-DR expression and resulted in the expansion of CD14+HLA-DRlow/- population. We found that lymphoma B cells produce IL-10 and supernatants from cultured lymphoma cells increased the CD14+HLA-DRlow/- population. Furthermore, we found that IL-10-induced CD14+HLA-DRlow/- monocytes inhibited the activation and proliferation of T cells. Taken together, these results suggest that elevated IL-10 serum levels contribute to increased numbers of immunosuppressive CD14+HLADRlow/- monocytes in B-cell NHL.

Original languageEnglish (US)
Article numbere328
JournalBlood Cancer Journal
Volume5
Issue number7
DOIs
StatePublished - Jul 31 2015

Fingerprint

B-Cell Lymphoma
Immunosuppressive Agents
Interleukin-10
Non-Hodgkin's Lymphoma
Monocytes
Lymphoma
Serum
Population
Phenotype
HLA-DR Antigens
Cultured Cells
Macrophages
T-Lymphocytes

ASJC Scopus subject areas

  • Hematology
  • Oncology

Cite this

IL-10 induces the development of immunosuppressive CD14+ HLA-DRlow/- monocytes in B-cell non-Hodgkin lymphoma. / Xiu, B.; Lin, Yi; Grote, D. M.; Ziesmer, S. C.; Gustafson, Michael; Maas, M. L.; Zhang, Z.; Dietz, Allan B; Porrata, L. F.; Novak, Anne J; Liang, A. B.; Yang, Z. Z.; Ansell, Stephen Maxted.

In: Blood Cancer Journal, Vol. 5, No. 7, e328, 31.07.2015.

Research output: Contribution to journalArticle

@article{7aaa714912924ae18e144e44758f3280,
title = "IL-10 induces the development of immunosuppressive CD14+ HLA-DRlow/- monocytes in B-cell non-Hodgkin lymphoma",
abstract = "The biological role of monocytes and macrophages in B-cell non-Hodgkin lymphoma (NHL) is not fully understood. We have previously reported that monocytes from patients with B-cell NHL have an immunosuppressive CD14+HLA-DRlow/- phenotype that correlates with a poor prognosis. However, the underlying mechanism by which CD14+HLA-DRlow/- monocytes develop in lymphoma is unknown. In the present study, we found that interleukin (IL)-10, which is increased in the serum of patients with B-cell NHL, induced the development of the CD4+HLA-DRlow/- population. Using peripheral blood samples from patients with B-cell NHL, we found that absolute numbers of CD14+ monocytic cells with an HLA-DRlow/- phenotype were higher than healthy controls and correlated with a higher International Prognostic Index score. IL-10 serum levels were elevated in lymphoma patients compared with controls and were associated with increased peripheral monocyte counts. Treatment of monocytes with IL-10 in vitro significantly decreased HLA-DR expression and resulted in the expansion of CD14+HLA-DRlow/- population. We found that lymphoma B cells produce IL-10 and supernatants from cultured lymphoma cells increased the CD14+HLA-DRlow/- population. Furthermore, we found that IL-10-induced CD14+HLA-DRlow/- monocytes inhibited the activation and proliferation of T cells. Taken together, these results suggest that elevated IL-10 serum levels contribute to increased numbers of immunosuppressive CD14+HLADRlow/- monocytes in B-cell NHL.",
author = "B. Xiu and Yi Lin and Grote, {D. M.} and Ziesmer, {S. C.} and Michael Gustafson and Maas, {M. L.} and Z. Zhang and Dietz, {Allan B} and Porrata, {L. F.} and Novak, {Anne J} and Liang, {A. B.} and Yang, {Z. Z.} and Ansell, {Stephen Maxted}",
year = "2015",
month = "7",
day = "31",
doi = "10.1038/bcj.2015.56",
language = "English (US)",
volume = "5",
journal = "Blood Cancer Journal",
issn = "2044-5385",
publisher = "Nature Publishing Group",
number = "7",

}

TY - JOUR

T1 - IL-10 induces the development of immunosuppressive CD14+ HLA-DRlow/- monocytes in B-cell non-Hodgkin lymphoma

AU - Xiu, B.

AU - Lin, Yi

AU - Grote, D. M.

AU - Ziesmer, S. C.

AU - Gustafson, Michael

AU - Maas, M. L.

AU - Zhang, Z.

AU - Dietz, Allan B

AU - Porrata, L. F.

AU - Novak, Anne J

AU - Liang, A. B.

AU - Yang, Z. Z.

AU - Ansell, Stephen Maxted

PY - 2015/7/31

Y1 - 2015/7/31

N2 - The biological role of monocytes and macrophages in B-cell non-Hodgkin lymphoma (NHL) is not fully understood. We have previously reported that monocytes from patients with B-cell NHL have an immunosuppressive CD14+HLA-DRlow/- phenotype that correlates with a poor prognosis. However, the underlying mechanism by which CD14+HLA-DRlow/- monocytes develop in lymphoma is unknown. In the present study, we found that interleukin (IL)-10, which is increased in the serum of patients with B-cell NHL, induced the development of the CD4+HLA-DRlow/- population. Using peripheral blood samples from patients with B-cell NHL, we found that absolute numbers of CD14+ monocytic cells with an HLA-DRlow/- phenotype were higher than healthy controls and correlated with a higher International Prognostic Index score. IL-10 serum levels were elevated in lymphoma patients compared with controls and were associated with increased peripheral monocyte counts. Treatment of monocytes with IL-10 in vitro significantly decreased HLA-DR expression and resulted in the expansion of CD14+HLA-DRlow/- population. We found that lymphoma B cells produce IL-10 and supernatants from cultured lymphoma cells increased the CD14+HLA-DRlow/- population. Furthermore, we found that IL-10-induced CD14+HLA-DRlow/- monocytes inhibited the activation and proliferation of T cells. Taken together, these results suggest that elevated IL-10 serum levels contribute to increased numbers of immunosuppressive CD14+HLADRlow/- monocytes in B-cell NHL.

AB - The biological role of monocytes and macrophages in B-cell non-Hodgkin lymphoma (NHL) is not fully understood. We have previously reported that monocytes from patients with B-cell NHL have an immunosuppressive CD14+HLA-DRlow/- phenotype that correlates with a poor prognosis. However, the underlying mechanism by which CD14+HLA-DRlow/- monocytes develop in lymphoma is unknown. In the present study, we found that interleukin (IL)-10, which is increased in the serum of patients with B-cell NHL, induced the development of the CD4+HLA-DRlow/- population. Using peripheral blood samples from patients with B-cell NHL, we found that absolute numbers of CD14+ monocytic cells with an HLA-DRlow/- phenotype were higher than healthy controls and correlated with a higher International Prognostic Index score. IL-10 serum levels were elevated in lymphoma patients compared with controls and were associated with increased peripheral monocyte counts. Treatment of monocytes with IL-10 in vitro significantly decreased HLA-DR expression and resulted in the expansion of CD14+HLA-DRlow/- population. We found that lymphoma B cells produce IL-10 and supernatants from cultured lymphoma cells increased the CD14+HLA-DRlow/- population. Furthermore, we found that IL-10-induced CD14+HLA-DRlow/- monocytes inhibited the activation and proliferation of T cells. Taken together, these results suggest that elevated IL-10 serum levels contribute to increased numbers of immunosuppressive CD14+HLADRlow/- monocytes in B-cell NHL.

UR - http://www.scopus.com/inward/record.url?scp=84989336939&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84989336939&partnerID=8YFLogxK

U2 - 10.1038/bcj.2015.56

DO - 10.1038/bcj.2015.56

M3 - Article

C2 - 26230952

AN - SCOPUS:84989336939

VL - 5

JO - Blood Cancer Journal

JF - Blood Cancer Journal

SN - 2044-5385

IS - 7

M1 - e328

ER -