Enhanced Expression of in B Cells of CLL Improves the Anti-Tumor Cytotoxic T Cell Response

The clinical progression of B cell chronic lymphocytic leukemia (CLL) is associated with immune cell dysfunction and a strong decrease of (), promoting the death of CLL cells. Here we investigated whether the reduction of impairs the immune response in CLL. We demonstrate that activated CD4+ T cells increase expression in CLL through CD40-CD40L signaling, which enhances the maturation and activity of cytotoxic T cells and, consequently, the apoptotic response of CLL cells. The cytotoxic response is facilitated by a depletion of the anti-inflammatory cytokine interleukin 10, targeted by . In vivo experiments in NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ mice confirmed that promotes the apoptotic death of CLL cells only when functional T cells are restored. Overall, our findings suggest that the reinstatement of in CLL cells could be an exploitable adjuvant therapeutic option for the treatment of CLL.