Search bioRxiv⌕ Search

Biology subjects

Barandalla-Revilla, L.

Publications and source records attributed to Barandalla-Revilla, L..

2 recordsLinked to original sources
bioRxiv2026

G-CSF associates with poor survival in cutaneous melanoma and promotes metastasis through coordinated effects on macrophages and tumor cells

Macrophage-melanoma interactions critically shape the tumor microenvironment, yet the cytokine networks driving this process remain incompletely understood. Among these, colony-stimulating factors--particularly granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF or CSF3)--regulate myeloid cell behavior during cancer progression, although their specific roles in melanoma remain unclear. Using co-culture systems of melanoma and monocyte-derived macrophages, we found that GM-CSF-primed macrophages induced robust G-CSF secretion and concurrent CSF3 upregulation in both cell compartments. Moreover, transcriptomic profiling of patient-derived tumor-associated macrophages (TAMs) confirmed elevated CSF3 and CSF3R expression in metastatic melanoma. Multiplex immunofluorescence analysis of a stage II-IV primary melanoma cohort (n=84) revealed increased G-CSF and CD114 expression in TAMs and tumor cells from patients who subsequently developed metastasis. High G-CSF levels in either TAMs or melanoma cells emerged as an independent prognostic factor for shorter disease-free and overall survival (p < 0.001). Mechanistically, G-CSF activated STAT1/STAT3 signaling in melanoma cells and promoted proliferation and invasion in a CD114-dependent manner. Of note, G-CSF drove monocyte differentiation toward a distinct inflammatory macrophage state characterized by STAT1/STAT3 activation and a pro-invasive secretory profile. Furthermore, melanoma cells conditioned by G-CSF-differentiated macrophages displayed increased in vivo lung colonization and enriched transcriptional programs linked to invasion and proliferation. Collectively, these findings establish the G-CSF/CD114 axis as a potential clinically relevant driver of melanoma metastasis and identify G-CSF as a novel independent prognostic biomarker. HIGHLIGHTSO_LIDespite its extended clinical use, G-CSF role in human melanoma remains undefined. C_LIO_LIHigh G-CSF expression in primary melanomas correlates with poor patient survival. C_LIO_LIG-CSF promotes melanoma cell invasion and proliferation through CD114 signaling. C_LIO_LIG-CSF drives macrophage differentiation toward a pro-tumoral phenotype. C_LIO_LIMelanoma cells conditioned by G-CSF-primed macrophages are more metastatic. C_LI

cancer biology↗
bioRxiv2025

Translating Genetics into Tissue: Inflammatory Cytokine-Producing TAMs and PD-L1 Tumor Expression as Poor Prognosis Factors in Cutaneous Melanoma

Myeloid cells within tumor microenvironments exhibit significant heterogeneity and play a critical role in influencing clinical outcomes. In this study, we investigated the infiltration of various myeloid cell subtypes in a cohort of cutaneous melanomas, revealing no significant correlation between myeloid cell densities and the occurrence of distant metastasis. We further examined the phenotypic characteristics of primary melanoma tumor-associated macrophages (TAMs) utilizing the seven-phenotype classification recently proposed by Ma et al., derived from extensive pan-cancer single-cell RNA-sequencing studies. First, we analyzed the transcriptomic profile of TAMs isolated from stage IV metastasizing primary melanomas, alongside melanoma-conditioned monocytes cultured in vitro, both supporting the inflammatory cytokine-producing macrophage phenotype. Next, we employed multicolor fluorescence confocal microscopy, to assess the expression of TAM phenotype markers at the protein level in a cohort of primary melanoma samples. Notably, markers indicative of the inflammatory TAM phenotype, quantified at single-cell level, were significantly enriched in metastasizing tumors, demonstrating an independent correlation with shorter disease-free and overall survival (log-rank test, p< 0.0002). Additionally, our screening of phenotype markers expression revealed that PD-L1 positivity in tumor cells, rather than in TAMs, was associated with poor prognosis, highlighting a novel aspect of the immune landscape in cutaneous melanoma.

cancer biology↗