Earnshaw and colleagues discover a tumor-intrinsic mechanism driven by glucocorticoid receptor (GR) activation, in which GR downregulates glycoprotein A repetitions predominant (GARP), thereby inhibiting TGFβ signaling and releasing CD8+ T cells to exert their antitumor activity. This mechanistic insight significantly advances our understanding of how GR shapes tumor immunity and highlights new avenues for overcoming immune checkpoint blockade resistance in melanoma and other cancers. See related article by Earnshaw et al., p. 345.
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