Changes in AXL and/or MITF melanoma subpopulations in patients receiving immunotherapy

• DOI: 10.1016/j.iotech.2024.101009
• Publication Date: 2024-11-15T02:29:30Z
• Authors: M. Willemsen; J. Bulgarelli; S.K. Chauhan; R.R. Lereim; D. Angeli; G. Grisendi; G. Krebbers; I. Davidson; J.A. Kyte; M. Guidoboni; R.M. Luiten; W.J. Bakker
• Keywords: Microphthalmia-associated transcription factor

Tumor heterogeneity is a hurdle to effective therapy, as illustrated by the 'mixed responses' frequently seen in immunotherapy-treated patients. Previously, AXL+ tumor cells were identified be highly resistant targeted whereas more differentiated MITF+ do respond RAF and MEK inhibitors. In this study, we analyzed explored presence of previously described or melanoma subpopulations metastatic tissues NanoString gene expression analysis, single-cell RNA sequencing situ multiplex immunofluorescence. Furthermore, how these correlate with immunological pressure response immunotherapy immunomodulating antibodies autologous lysate-loaded dendritic cell vaccination. Our data demonstrate large interpatient variability variable therapy-induced changes independent type therapy. We identify both at mRNA level protein level, that are significantly decreased upon immunotherapy, while numbers stable. showed most significant inverse correlation CD8+ T cells. patient cohort also shows immunotherapy-induced abundance did not improved survival. Overall, study suggests tumors efficiently may resistant, analogous their