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Abstract
Imiquimod is a TLR agonist that is used as an antitumor agent, mainly against skin tumors. Its clinical benefits are well described in several studies; however, the mechanisms behind its antitumor effects are not completely understood. In this issue of the JCI, Drobits and colleagues demonstrate that topical application of imiquimod suppresses cutaneous melanoma by TLR7-dependent recruitment and transformation of plasmacytoid dendritic cells into killer cells; this occurs independently of conventional adaptive immune mechanisms.
Authors
Sonia Jiménez-Baranda, Inês Pires Silva, Nina Bhardwaj
Figure 1
Mechanism of imiquimod-mediated tumor cell killing by pDCs.
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(i) Skin application of imiquimod acts on mast cells through TLR7, inducing the secretion of CCL2. (ii) CD8α+ pDCs migrate to the skin toward CCL2 while at the same time being exposed to imiquimod. Imiquimod-stimulated pDCs produce high levels of type I IFNs, which have several effects. First (iii), in a paracrine loop, type I IFNs induce pDCs to kill tumor cells through upregulation of expression and/or secretion of cytolytic molecules such as TRAIL and granzyme B. Second (iv), type I IFNs induce on melanoma cells the expression of the receptor for TRAIL (DR5), which makes them susceptible to killing by TRAIL-expressing pDCs.
Copyright © 2022 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)