429 Targeting mast-cell plasticity re-shapes the tumor microenvironment of melanoma

The incidence of malignant melanoma is steadily rising. Due to its metastatic potential the cancer has a poor prognosis and responsible for 80% patients with skin dying. treatment was revolutionized by development new immunotherapies, however long-term responses are still limited few complete remissions rare due resistance therapy. Therefore, there need therapeutic options melanoma. Resistance therapy in linked an increase phenotypic heterogeneity cells their response pro-inflammatory signals from tumor microenvironment (TME). Within TME melanoma, accumulation MCs been found, especially areas regression. Since plastic regard functions can secrete various mediators, we currently investigating impact endogenous factors how they MC thereby mediate control To decipher role plasticity progression, generated mast murine femur (BMMCs) matured them medium containing IL-3 stem cell factor. simulate TME, were stimulated alarmin IL-33 combination TLR-agonists. RNA Sequencing showed strong enrichment genes involved cytokine-mediated signaling pathways BMMC IL-33. combinations stimuli acted antagonistically or synergistically on regarding secretion cytokines that detected supernatant. Upon highest concentration CCL3, CCL4 CCL22, which play crucial recruitment immune cells. Supernatant also inhibitory effect B16 vitro. In vivo experiments using model mast-cell deficient Mcpt5-cre RDTA mice combined tumors IL33R-TLR2/6 inhibits progression dependent manner, modulating TME.