Soluble and Membrane-Bound TGF-β-Mediated Regulation of Intratumoral T Cell Differentiation and Function in B-Cell Non-Hodgkin Lymphoma

Zhi Zhang Yang, Deanna M. Grote, Steven C. Ziesmer, Bing Xiu, Nicole R. Yates, Frank J. Secreto, Lucy S. Hodge, Thomas Elmer Witzig, Anne J Novak, Stephen Maxted Ansell

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

While the effect of TGF-β on malignant B cells in non-Hodgkin lymphoma (NHL) has been previously evaluated, studies to specifically define the role of TGF-β in tumor immunity in B-cell NHL are limited. We found that soluble TGF-β, secreted by both lymphoma cells and intratumoral T cells, is present in the serum of patients with B-cell NHL. Soluble TGF-β promoted regulatory T (Treg) cells by enhancing expression of Foxp3 in CD4+ T cells and suppressed effector helper T (TH) cells by inhibiting expression of IFN-γ and IL-17. Blockade of the IL-2 signaling pathway diminished the effect of soluble TGF-β on T cell differentiation. Furthermore, we found that membrane-bound TGF-β is expressed specifically on the surface of malignant B cells in B-cell NHL. TGF-β was able to bind to the surface of lymphoma B cells through an interaction with heparan sulfate (HS) but not through the TGF-β receptor. We showed that pretreatment of lymphoma B cells with TGF-β significantly inhibits the proliferation and cytokine production of intratumoral T cells. Taken together, these results suggest that tumor-associated soluble and membrane-bound TGF-β are involved in the regulation of intratumoral T cell differentiation and function in B-cell NHL.

Original languageEnglish (US)
Article numbere59456
JournalPLoS One
Volume8
Issue number3
DOIs
StatePublished - Mar 15 2013

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non-Hodgkin lymphoma
T-cells
B-Cell Lymphoma
cell differentiation
Non-Hodgkin's Lymphoma
B-lymphocytes
Cell Differentiation
T-lymphocytes
Cells
Membranes
T-Lymphocytes
Regulatory T-Lymphocytes
lymphoma
Lymphoma
B-Lymphocytes
Heparitin Sulfate
Interleukin-17
Tumors
Helper-Inducer T-Lymphocytes
Cell Communication

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Soluble and Membrane-Bound TGF-β-Mediated Regulation of Intratumoral T Cell Differentiation and Function in B-Cell Non-Hodgkin Lymphoma. / Yang, Zhi Zhang; Grote, Deanna M.; Ziesmer, Steven C.; Xiu, Bing; Yates, Nicole R.; Secreto, Frank J.; Hodge, Lucy S.; Witzig, Thomas Elmer; Novak, Anne J; Ansell, Stephen Maxted.

In: PLoS One, Vol. 8, No. 3, e59456, 15.03.2013.

Research output: Contribution to journalArticle

Yang, Zhi Zhang ; Grote, Deanna M. ; Ziesmer, Steven C. ; Xiu, Bing ; Yates, Nicole R. ; Secreto, Frank J. ; Hodge, Lucy S. ; Witzig, Thomas Elmer ; Novak, Anne J ; Ansell, Stephen Maxted. / Soluble and Membrane-Bound TGF-β-Mediated Regulation of Intratumoral T Cell Differentiation and Function in B-Cell Non-Hodgkin Lymphoma. In: PLoS One. 2013 ; Vol. 8, No. 3.
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