Mast cell phenotypic remodeling toward a PD-1-positive, Chymase-negative phenotype is associated with metastatic melanoma and poor survival.
4 affiliations
- 1Unidad de Investigación Médica en Inmunología, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de México, México.
- 2Coordinación de Investigación en Salud, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de México, México.
- 3Unidad de Investigación Médica en Inmunoquímica, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de México, México.
- 4Unidad de Investigación en Virología y Cáncer, Hospital Infantil de México Federico Gómez, Ciudad de México, México.
Abstract
Mast cells (MCs) display phenotypic heterogeneity across tissues and disease contexts, yet their relevance in melanoma remains unclear. Here, we investigated MC phenotypic programs associated with melanoma progression using high-dimensional phenotyping of MCs co-cultured with melanoma spheroids, trajectory inference, and transcriptomic analyzes. Human melanoma tissues showed differences in MC phenotypic composition despite comparable abundance between outcome groups, with metastatic melanomas enriched for Tryptase⁺ Chymase⁻ MCs. Melanoma exposure induced MC phenotypic remodeling, characterized by loss of lineage- and effector-associated features and increased PD-1 expression, with more pronounced changes following metastatic melanoma co-culture. Trajectory analysis was consistent with a continuum toward a PD-1⁺ Chymase⁻ phenotype, which was detected in melanoma tissues and enriched within intratumoral regions of metastatic melanomas. Experimentally defined protein changes were used to derive two MC-associated transcriptomic signatures with opposing clinical associations, reflecting lineage- and effector-enriched versus melanoma-remodeled programs. The MC-LE signature was associated with favorable survival and interferon-responsive pathways, whereas the MC-MR signature was associated with poorer survival and tumor-associated pathways. These transcriptomic associations extended beyond melanoma across multiple TCGA cancer cohorts, and independent analysis of MCs from healthy skin, basal cell carcinoma, and melanoma showed corresponding differences in MC-LE-related features. Together, these findings support distinct mast cell phenotypic programs associated with melanoma progression and identify a PD-1⁺ Chymase⁻ MC phenotype enriched in metastatic disease and linked to transcriptomic features of poor survival.
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BibTeX
@article{gajon2026mast,
title = {{Mast cell phenotypic remodeling toward a PD-1-positive, Chymase-negative phenotype is associated with metastatic melanoma and poor survival.}},
author = {Julián A Gajón and Laura C Bonifaz and Ezequiel Fuentes-Panana and Samira Muñoz-Cruz},
journal = {Oncoimmunology},
year = {2026},
month = oct,
doi = {10.1080/2162402x.2026.2752644},
url = {https://europepmc.org/article/MED/42912494},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Mast cell phenotypic remodeling toward a PD-1-positive, Chymase-negative phenotype is associated with metastatic melanoma and poor survival.
AU - Julián A Gajón
AU - Laura C Bonifaz
AU - Ezequiel Fuentes-Panana
AU - Samira Muñoz-Cruz
PY - 2026
DA - 2026/10/23
JO - Oncoimmunology
DO - 10.1080/2162402x.2026.2752644
UR - https://europepmc.org/article/MED/42912494
AB - Mast cells (MCs) display phenotypic heterogeneity across tissues and disease contexts, yet their relevance in melanoma remains unclear. Here, we investigated MC phenotypic programs associated with melanoma progression using high-dimensional phenotyping of MCs co-cultured with melanoma spheroids, trajectory inference, and transcriptomic analyzes. Human melanoma tissues showed differences in MC phenotypic composition despite comparable abundance between outcome groups, with metastatic melanomas enriched for Tryptase⁺ Chymase⁻ MCs. Melanoma exposure induced MC phenotypic remodeling, characterized by loss of lineage- and effector-associated features and increased PD-1 expression, with more pronounced changes following metastatic melanoma co-culture. Trajectory analysis was consistent with a continuum toward a PD-1⁺ Chymase⁻ phenotype, which was detected in melanoma tissues and enriched within intratumoral regions of metastatic melanomas. Experimentally defined protein changes were used to derive two MC-associated transcriptomic signatures with opposing clinical associations, reflecting lineage- and effector-enriched versus melanoma-remodeled programs. The MC-LE signature was associated with favorable survival and interferon-responsive pathways, whereas the MC-MR signature was associated with poorer survival and tumor-associated pathways. These transcriptomic associations extended beyond melanoma across multiple TCGA cancer cohorts, and independent analysis of MCs from healthy skin, basal cell carcinoma, and melanoma showed corresponding differences in MC-LE-related features. Together, these findings support distinct mast cell phenotypic programs associated with melanoma progression and identify a PD-1⁺ Chymase⁻ MC phenotype enriched in metastatic disease and linked to transcriptomic features of poor survival.
SN - 2162-4011
SN - 2162-402X
ER -