1254 Topical corticosteroids stimulate T cell-dependent melanoma growth control

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