2026-06-27T11:24:30Zhttps://docta.ucm.es/rest/oai/request
oai:docta.ucm.es:20.500.14352/47532024-10-10T17:35:51Zcom_20.500.14352_14col_20.500.14352_15
Docta Complutense author Gutiérrez Seijo, Alba author García Martínez, Elena author Barrio Alonso, Celia author Pareja Malagón, Miriam author Acosta Ocampo, Alejandra author Fernández Santos, María Eugenia author Puig Kröger, Amaya author Parra Blanco, Verónica author Mercader Cidoncha, Enrique author Márquez Rodas, Iván author Avilés Izquierdo, José Antonio author Samaniego, Rafael author Sánchez-Mateos Rubio, María Paloma 2023-06-16T14:20:38Z 2023-06-16T14:20:38Z 2021-08-05 2072-6694 10.3390/cancers13163943 https://hdl.handle.net/20.500.14352/4753 https://doi.org/10.3390/cancers13163943 https://www.mdpi.com/2072-6694/13/16/3943/htm 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. eng Atribución 3.0 España CCL20/TNF/VEGFA Cytokine Secretory Phenotype of Tumor-Associated Macrophages Is a Negative Prognostic Factor in Cutaneous Melanoma journal article URL https://docta.ucm.es/bitstreams/96ef61f0-2199-493c-a119-a8d291d6484b/download File MD5 5bb6c85b0634297461767764ee9bb4d7 2122069 application/pdf cancers-13-03943-v2.pdf