Chronic lymphocytic leukemia of B-cell origin (B-CLL) is the most common adult leukemia in the Western hemisphere. B-CLL is considered as a prototypic disease undergoing immune evasion as the malignant cells lack important accessory and co-stimulatory molecules. Thus, despite their expression of high levels of surface MHC class I and II molecules, which presumably present tumorassociated antigenic epitopes, the leukemic cells tend to induce tumor-specific T-cell anergy. Typically, activated T cells from patients show a significantly reduced expression of CD40 ligand (CD154) or are completely CD154-negative [13] . As a consequence, T cells from B-CLL patients cannot activate cells through the CD40 receptor. This interaction, however, is essential for CD40 signaling and subsequent induction of other immune accessory molecules like CD80 and CD86, which increase the antigen-presenting capacity of normal and B-CLL cells. On the other hand, the EBV-specific cellular immunity is relatively intact in these patients [2] . To overcome the dysfunction of potentially tumor-reactive T cells from patients with B-CLL, several approaches have been developed relying on the stimulation of B-CLL cells through the CD40 pathway, including the ectopic expression of CD154 on the leukemic cells, and aiming at the selfstimulation of these cells [14] [15] [16] [17] . In summary, immunotherapy of B-CLL is promising and CD154 is a potential candidate molecule to improve the patients' immune status and, eventually, the clinical outcome.