Glucocorticoids Unleash Immune-dependent Melanoma Control through Inhibition of the GARP/TGFβ Axis.

ABSTRACT: Half of patients with advanced melanoma fail to benefit from immune checkpoint blockade, and novel treatments are urgently required. Testing topical medications for anticancer activity in an immunotherapy-resistant murine melanoma model, we found that, counterintuitively, glucocorticoids (GCs) elicit rapid cytotoxic T lymphocyte (CTL)-dependent tumor control. Genetic ablation of the GC receptor in different cellular compartments revealed that GCs acted not on immune cells but directly on tumor cells to downregulate the expression of glycoprotein A repetitions predominant (GARP). This inhibited TGFβ signaling and unleashed CTL killing. In agreement, GCs stimulated tumor control in multiple cancer models but only if the tumors also responded to pharmacologic inhibition of TGFβ signaling. Fur

SUBMITTER: Earnshaw CH 

PROVIDER: S-EPMC7618275 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature