Tumor environments are often associated with immunosuppressive factors, such as interleukin 10 (IL-10) and transforming growth factor-β1 (TGF-β1), that limit antitumor immune responses. In Science Signaling, Merline et al. show that soluble decorin, a matrix proteoglycan, promotes antitumor immunity by blocking TGF-β1 signaling and limiting IL-10 release. Macrophages express soluble decorin after stimulation with lipopolysaccharide. Decorin binds to Toll-like receptors 2 and 4, leading to higher expression of Pdcd4, which encodes the translational repressor PDCD4 that can suppress IL-10 production. However, PDCD4 is under translational regulation by the microRNA miR-21, which is activated by TGF-β1 signaling. Decorin-mediated inhibition of TGF-β1 relieves the suppression of PDCD4 by miR-21 and thereby decreases the secretion of immunosuppressive IL-10. Mice that ectopically express decorin have enhanced proinflammatory antitumor responses. It remains unknown whether cancer patients can likewise benefit from decorin treatment.
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Dempsey, L. Regulation by proteoglycans. Nat Immunol 13, 19 (2012). https://doi.org/10.1038/ni.2200
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DOI: https://doi.org/10.1038/ni.2200