Thus, antitumor effects of activated macrophages must overcome the proliferative and anti-apoptotic effects of these stimuli on tumor cells.94 In agreement with this observation, the lack of TIR8 receptor which normally inhibits the signaling of TLRs, results in earlier and more aggressive CLL in TCL1-tg/Tir8−/− crossed mice.95 Nevertheless, ligands for TLRs other than TLR9 might provide better and more specific activation of macrophages, resulting in improvement of CD40-based immunotherapy. This evidence concerns the gene CD40 and B-cell chronic lymphocytic leukemia.