469 Analyzing resistance of AXL- and/or MITF-expressing melanoma cells to immunotherapy

Tumor heterogeneity is commonly seen in melanoma patients and a hurdle to effective therapy as illustrated by the “mixed responses” frequently immunotherapy-treated patients. Previously, AXL+ cells were identified be highly resistant targeted therapy, whereas more differentiated MITF+ responded well RAF/MEK inhibitors. This study aimed identify if show intrinsic resistance immunotherapy, these are than subpopulations. Concomitantly, we validate subpopulations at protein level correlate immunological pressure. We analyzed presence of cell populations metastatic tissues scRNAseq multiplex immunofluorescence, their phenotypic changes after immunomodulating antibodies or autologous tumor lysate-loaded dendritic vaccination. Our data demonstrate large inter patient variability variable therapy-induced changes, independent type therapy. Treatment with anti-CTLA4 vaccines did not exclusively select for AXL- cells, treatment. Immunotherapy-induced abundance MITF- improved survival. showed weak inverse correlation CD8+ T suggesting that may immunogenic. highlights seem immunotherapy However, immunoreactivity increased towards MITF-expressing therefore likely respond better immunotherapy.