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...
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| Format: | Article |
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Frontiers Media S.A.
2025-05-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1587545/full |
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| author | Celia Barrio-Alonso Celia Barrio-Alonso Alicia Nieto-Valle Alicia Nieto-Valle Alicia Nieto-Valle Lucía Barandalla-Revilla Lucía Barandalla-Revilla José Antonio Avilés-Izquierdo Verónica Parra-Blanco Paloma Sánchez-Mateos Paloma Sánchez-Mateos Rafael Samaniego |
| author_facet | Celia Barrio-Alonso Celia Barrio-Alonso Alicia Nieto-Valle Alicia Nieto-Valle Alicia Nieto-Valle Lucía Barandalla-Revilla Lucía Barandalla-Revilla José Antonio Avilés-Izquierdo Verónica Parra-Blanco Paloma Sánchez-Mateos Paloma Sánchez-Mateos Rafael Samaniego |
| author_sort | Celia Barrio-Alonso |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-b68c7c527389488eb92b4bb10325dd59 |
| institution | OA Journals |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-b68c7c527389488eb92b4bb10325dd592025-08-20T02:14:22ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-05-011610.3389/fimmu.2025.15875451587545Translating genetics into tissue: inflammatory cytokine-producing TAMs and PD-L1 tumor expression as poor prognosis factors in cutaneous melanomaCelia Barrio-Alonso0Celia Barrio-Alonso1Alicia Nieto-Valle2Alicia Nieto-Valle3Alicia Nieto-Valle4Lucía Barandalla-Revilla5Lucía Barandalla-Revilla6José Antonio Avilés-Izquierdo7Verónica Parra-Blanco8Paloma Sánchez-Mateos9Paloma Sánchez-Mateos10Rafael Samaniego11Unidad de Microscopía Confocal, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, SpainLaboratorio de Inmuno-oncología, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, SpainUnidad de Microscopía Confocal, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, SpainLaboratorio de Inmuno-oncología, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, SpainDepartamento de Inmunología, Universidad Complutense de Madrid, Madrid, SpainUnidad de Microscopía Confocal, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, SpainLaboratorio de Inmuno-oncología, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, SpainServicio de Dermatología, Hospital General Universitario Gregorio Marañón, Madrid, SpainServicio de Anatomía Patológica, Hospital General Universitario Gregorio Marañón, Madrid, SpainLaboratorio de Inmuno-oncología, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, SpainDepartamento de Inmunología, Universidad Complutense de Madrid, Madrid, SpainUnidad de Microscopía Confocal, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, SpainMyeloid 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.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1587545/fulltumor-associated macrophagesinflammatory cytokine-producing TAMsprognostic factorPD-L1myeloid cellscutaneous melanoma |
| spellingShingle | Celia Barrio-Alonso Celia Barrio-Alonso Alicia Nieto-Valle Alicia Nieto-Valle Alicia Nieto-Valle Lucía Barandalla-Revilla Lucía Barandalla-Revilla José Antonio Avilés-Izquierdo Verónica Parra-Blanco Paloma Sánchez-Mateos Paloma Sánchez-Mateos Rafael Samaniego Translating genetics into tissue: inflammatory cytokine-producing TAMs and PD-L1 tumor expression as poor prognosis factors in cutaneous melanoma Frontiers in Immunology tumor-associated macrophages inflammatory cytokine-producing TAMs prognostic factor PD-L1 myeloid cells cutaneous melanoma |
| title | Translating genetics into tissue: inflammatory cytokine-producing TAMs and PD-L1 tumor expression as poor prognosis factors in cutaneous melanoma |
| title_full | Translating genetics into tissue: inflammatory cytokine-producing TAMs and PD-L1 tumor expression as poor prognosis factors in cutaneous melanoma |
| title_fullStr | Translating genetics into tissue: inflammatory cytokine-producing TAMs and PD-L1 tumor expression as poor prognosis factors in cutaneous melanoma |
| title_full_unstemmed | Translating genetics into tissue: inflammatory cytokine-producing TAMs and PD-L1 tumor expression as poor prognosis factors in cutaneous melanoma |
| title_short | Translating genetics into tissue: inflammatory cytokine-producing TAMs and PD-L1 tumor expression as poor prognosis factors in cutaneous melanoma |
| title_sort | translating genetics into tissue inflammatory cytokine producing tams and pd l1 tumor expression as poor prognosis factors in cutaneous melanoma |
| topic | tumor-associated macrophages inflammatory cytokine-producing TAMs prognostic factor PD-L1 myeloid cells cutaneous melanoma |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1587545/full |
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