IL-10-producing B cells in differentiated thyroid cancer suppress the effector function of T cells but improve their survival upon activation.

ABSTRACT

Despite having favorable prognosis, patients with differentiated thyroid carcinoma (DTC) still suffer from reduced lifespan due to recurrences, metastasis, and dedifferentiation. Regulatory B (Breg) cells are essential to the maintenance of peripheral tolerance, but upregulated Breg response may impede the clearance of pathogens and tumor cells. Here, we found that in PBMCs, the frequency of IL-10+ circulating B cells ex vivo and following stimulation was similar between DTC patients and healthy controls. However, in resected tumor, the frequency of IL-10+ B cells was significantly elevated and was positively correlated with the frequency of tumor-infiltrating CD4+Foxp3+ T cells. The quantity of IL-10 produced by B cells was significantly higher in DTC patients than in controls. Moreover, each IL-10-producing B cell in DTC patients produced more IL-10 than the counterparts in healthy controls. This IL-10+ subset was enriched in the CD27+ fraction. Under an in vitro setting, CD27+ B cells inhibited IFN-γ expression from CD4+ T cells and IFN-γ, perforin, and granzyme B expression from CD8+ T cells. Suppression of IL-10 could rescue IFN-γ production but was unable to completely rescue perforin and granzyme B expression. The proliferation of CD4+ and CD8+ T cells, on the other hand, was not affected by CD27+ B cells. Interestingly, CD27+ B cells improved the survival of activated CD4+ and CD8+ T cells, in an IL-10-dependent manner. In addition, the phosphorylation level of STAT3 and Erk was examined in CD27+ B cells. Unstimulated CD27+ B cells presented low STAT3 and Erk phosphorylation in both healthy controls and DTC patients, with no significant difference between the two groups. Overall, this study suggests that B cell-mediated IL-10 production can exert complex effects toward autologous T cells.