title: Soluble and membrane-bound TGF-β-mediated regulation of intratumoral T cell differentiation and function in B-cell non-Hodgkin lymphoma.
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 (T(reg)) cells by enhancing expression of Foxp3 in CD4(+) T cells and suppressed effector helper T (T(H)) 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.
authors.affiliation: Division of Hematology, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minnesota, United States of America. yang.zhizhang@mayo.edu
authors.forename: Zhi-Zhang
authors.initials: ZZ
authors.lastname: Yang
authors.forename: Deanna M
authors.initials: DM
authors.lastname: Grote
authors.forename: Steven C
authors.initials: SC
authors.lastname: Ziesmer
authors.forename: Bing
authors.initials: B
authors.lastname: Xiu
authors.forename: Nicole R
authors.initials: NR
authors.lastname: Yates
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Secreto
authors.forename: Lucy S
authors.initials: LS
authors.lastname: Hodge
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Witzig
authors.forename: Anne J
authors.initials: AJ
authors.lastname: Novak
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Ansell
mesh_terms: D001402:B-Lymphocytes / Q000166:cytology* / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D008228:Lymphoma, Non-Hodgkin / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D012995:Solubility; D013601:T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D059016:Tumor Microenvironment / Q000187:drug effects / Q000276:immunology
chemical_list: D007376:Interleukin-2; D016212:Transforming Growth Factor beta
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