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- W4366183991 abstract "Melanoma is the deadliest form of skin cancer. Treatment with immune checkpoint blockade (ICB) has transformed outcomes. However, half of melanoma patients do not derive benefit and many face toxicities. Patients that do not respond typically have immunologically “cold” tumors. We therefore sought to test a range of widely-used topical treatments for their ability to increase the immunogenic properties of mouse models of melanoma. We identified an intradermal murine melanoma model that is fully unresponsive to ICB, including the combination of anti-PD1 and anti-CTLA4 blockade. Across a number of different treatments, topical corticosteroids uniquely promoted tumor control. Remarkably, after just two doses, glucocorticoid-treated tumors shrank, whereas control-treated tumors doubled in volume (p<0.0001). Intriguingly, this effect was completely lost in lymphocyte deficient mice, or in mice depleted of CD8+ T cells, uncovering a key role for T cells in corticosteroid-induced tumor control. Genetic ablation of the glucocorticoid receptor in tumor cells, but not in the lymphoid or myeloid compartment, abrogated the effects of corticosteroids, suggesting they act directly on tumor cells to elicit anti-tumor immunity. Analysis of patient transcriptomes pan-cancer revealed a negative association between glucocorticoid receptor expression and survival. However, consistent with our in vivo data, melanoma patients with high glucocorticoid receptor expression survived longer than those with low expression (median survival 8.95 years vs 4.18 years, hazard ratio 0.48, p=0.00039). Ongoing work aims to dissect the cellular and molecular mechanisms underlying this effect of topical corticosteroid treatment, and to investigate the relevance in human melanoma. Given the widespread use of corticosteroids in patients receiving ICB, these unexpected findings may have significant clinical impact." @default.
- W4366183991 created "2023-04-19" @default.
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- W4366183991 date "2023-05-01" @default.
- W4366183991 modified "2023-09-27" @default.
- W4366183991 title "1254 Topical corticosteroids stimulate T cell-dependent melanoma growth control" @default.
- W4366183991 doi "https://doi.org/10.1016/j.jid.2023.03.1268" @default.
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