Toll-like receptor agonists plus tumor antigen, or interferon γ, may be therapeutically active for cutaneous T-cell lymphoma. The major populations of human dendritic cells include myeloid dendritic cells (mDCs) that express TLR8 and plasmacytoid dendritic cells (pDCs) that express TLRs 7 and 9. In the study by Kim et al, vaccination with CpG-ODNs, which are agonists for TLR9, was used to prime pDCs simultaneously with local radiation to active CTCL skin lesions. Other TLR agonists in clinical development for CTCL include imiquimod, an agonist for TLR7, and resiquimod, an agonist for TLR8. These TLR agonists may produce synergistic activation of the immune response with IFN γ. Similarly, there may be additive or synergistic stimulation of an antitumor response when a TLR agonist is used in combination with apoptotic tumor cells. On activation of mDCs, IL-12 and IL-15 are produced while activation of pDCs results in production of IFNα. There is also up-regulation of the co-stimulatory molecules CD80 and CD86. Induction of cytokines and up-regulation of co-stimulatory molecules are highly beneficial for the adaptive immune response leading to the development of antitumor cytotoxic T cells. Professional illustration by Kenneth X. Probst.