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Updated: Jan 14, 2026
A 3D Organotypic Melanoma Spheroid Skin Model
Published on: May 18, 2018
Adverse prognosis of GM-CSF expression in human cutaneous melanoma
Elena García-Martínez1, Alicia Nieto-Valle2, Celia Barrio-Alonso1
1Unidad de Microscopía Confocal, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain; Laboratorio de Inmuno-oncología, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.
Background:
GM-CSF, a myeloid-priming cytokine, exhibits context-dependent effects on tumor growth and, despite its clinical use, its role in human melanoma remains undefined.
Methods:
A stage II-IV primary melanoma cohort (n = 80) was interrogated for GM-CSF/GM-CSFR expression at the single-cell level in tumor-associated macrophages (TAMs) and tumor cells (TCs). Invasion, survival and lung colonization assays were used to determine the pro-tumoral role of GM-CSF, and RNA-seq to analyze transcriptomic profiles.
Results:
GM-CSF was significantly enriched in TAMs and TCs of primary cutaneous melanoma samples from patients who subsequently developed metastasis, compared with non-metastasizing ones, correlating with reduced disease-free and overall survival (p < 0.0001). GM-CSF receptor subunits were present in both cell types and their expression did not correlate with clinical outcomes. GM-CSF activated non-canonical signaling pathways in TCs, promoted their invasiveness and enhanced in vivo lung colonization in a murine model. GM-CSF-primed macrophages secreted higher levels of inflammatory cytokines upon interaction with melanoma cells than those unprimed or primed with M-CSF. Reciprocally, RNA-seq analyses revealed a broader transcriptional reprogramming in melanoma cells exposed to GM-CSF-primed macrophages.
Conclusions:
Our findings highlight a potentially pro-tumorigenic GM-CSF-driven paracrine axis in patients with poor-prognosis melanoma, supporting therapeutic strategies aimed at disrupting this signaling network.
