ABSTRACT
While the effect of TGF-ß on malignant B cells in non-Hodgkin lymphoma (NHL) has been previously evaluated, studies to specifically define the role of TGF-ß in tumor immunity in B-cell NHL are limited. We found that soluble TGF-ß, secreted by both lymphoma cells and intratumoral T cells, is present in the serum of patients with B-cell NHL. Soluble TGF-ß 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-ß on T cell differentiation. Furthermore, we found that membrane-bound TGF-ß is expressed specifically on the surface of malignant B cells in B-cell NHL. TGF-ß was able to bind to the surface of lymphoma B cells through an interaction with heparan sulfate (HS) but not through the TGF-ß receptor. We showed that pretreatment of lymphoma B cells with TGF-ß significantly inhibits the proliferation and cytokine production of intratumoral T cells. Taken together, these results suggest that tumor-associated soluble and membrane-bound TGF-ß are involved in the regulation of intratumoral T cell differentiation and function in B-cell NHL.
