RT Journal Article
T1 CCL20/TNF/VEGFA Cytokine Secretory Phenotype of Tumor-Associated Macrophages Is a Negative Prognostic Factor in Cutaneous Melanoma
A1 Gutiérrez Seijo, Alba
A1 García Martínez, Elena
A1 Barrio Alonso, Celia
A1 Pareja Malagón, Miriam
A1 Acosta Ocampo, Alejandra
A1 Fernández Santos, María Eugenia
A1 Puig Kröger, Amaya
A1 Parra Blanco, Verónica
A1 Mercader Cidoncha, Enrique
A1 Márquez Rodas, Iván
A1 Avilés Izquierdo, José Antonio
A1 Samaniego, Rafael
A1 Sánchez-Mateos Rubio, María Paloma
AB TAMs constitute a large fraction of infiltrating immune cells in melanoma tissues, but their significance for clinical outcomes remains unclear. We explored diverse TAM parameters in clinically relevant primary cutaneous melanoma samples, including density, location, size, and polarization marker expression; in addition, because cytokine production is a hallmark of macrophages function, we measured CCL20, TNF, and VEGFA intracellular cytokines by single-cell multiparametric confocal microscopy. The Kaplan–Meier method was used to analyze correlation with melanoma-specific disease-free survival and overall survival. No significant correlations with clinical parameters were observed for TAM density, morphology, or location. Significantly, higher contents of the intracellular cytokines CCL20, TNF, and VEGFA were quantified in TAMs infiltrating metastasizing compared to non-metastasizing skin primary melanomas (p < 0.001). To mechanistically explore cytokine up-regulation, we performed in vitro studies with melanoma-conditioned macrophages, using RNA-seq to explore involved pathways and specific inhibitors. We show that p53 and NF-κB coregulate CCL20, TNF, and VEGFA in melanoma-conditioned macrophages. These results delineate a clinically relevant pro-oncogenic cytokine profile of TAMs with prognostic significance in primary melanomas and point to the combined therapeutic targeting of NF-kB/p53 pathways to control the deviation of TAMs in melanoma.
PB MPDI
SN 2072-6694
YR 2021
FD 2021-08-05
LK https://hdl.handle.net/20.500.14352/4753
UL https://hdl.handle.net/20.500.14352/4753
LA eng
NO Instituto de Salud Carlos III (ISCIII)/ MINECO/ FEDER
NO Cancer Research UK, FCAECC
DS Docta Complutense
RD 20 abr 2025