ABSTRACT
Dendritic cells (DCs) are highly potent initiators of adaptive immune responses and, as such, represent promising tools for immunotherapeutic applications. Despite their potential, the current efficacy of DC-based immunotherapies is poor. CD137 ligand (CD137L) signaling has been used to derive a novel type of DCs from human peripheral blood monocytes, termed CD137L-DCs. Here, we report that CD137L-DCs induce more potent cytotoxic T-cell responses than classical DCs (cDCs). Furthermore, in exploring several DC maturation factors for their ability to enhance the potency of CD137L-DCs, we found the combination of interferon γ (IFNγ) and the mixed Toll-like receptor (TLR)7/8 agonist R848, to display the highest efficacy in potentiating the T-cell co-stimulatory activity of CD137L-DCs. Of particular importance, CD137L-DCs were found to be more efficient than cDCs in activating autologous T cells targeting the cytomegalovirus (CMV)-derived protein pp65. Specifically, CD137L-DC-stimulated T cells were found to secrete higher levels of IFNγ and killed 2-3 times more HLA-matched, pp65-pulsed target cells than T cells activated by cDCs. Finally, in addition to stimulating CD8+ T cells, CD137L-DCs efficiently activated CD4+ T cells. Taken together, these findings demonstrate the superior potency of CD137L-stimulated DCs in activating CMV-specific, autologous T cells, and encourage the further development of CD137L-DCs for antitumor immunotherapy.
