Dr Kerrie Marie will talk about an embryonic approach to uncover new mechanisms of melanoma progression.

TOPICS COVERED

Abstract: Melanoma, a cancer of the melanocyte, is highly metastatic and can evade therapies through non-genetic means. The cancer cell state(s) driving both phenotypes resemble the embryonic neural crest. However, the specific reinitiated neural crest cell states are unknown. Here we present high-resolution single-cell RNA-seq profiles of Dct-GFP+ murine neural crest cells of the melanocytic lineage. We leverage this with computational analyses to discover clinically relevant melanoma neural-crest cell states in patient tumors and in murine metastatic evolution. We predict that melanocytes arise from highly plastic Schwann-cell precursors (SCPs) via a mesenchymal-like (Mes) state. We show tumors expressing SCP genes predict clinical responses to immune checkpoint inhibitor therapy. We identify melanoblast/melanoma cells that simultaneously express multiple neural crest lineage markers, suggesting a lack of fate restriction. These hybrid cells are enriched in early metastasis and interferon signaling is implicated in their evolution. Our work pin-points lineage-specific phenotypes that underlie melanoma progression and tumor evolution.

WHO SHOULD ATTEND?

Pathologists of all levels.

SPEAKER

Dr Kerrie Marie from University of Manchester

For more informatin, please contact: [email protected]