---
title: "PD‑1–positive, Chymase‑negative mast cell phenotype links to metastatic melanoma and worse survival"
id: "pubmed-42912494"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42912494"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42912494/"
doi: "10.1080/2162402X.2026.2752644"
published_at: "2026-10-23T22:55:27.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# PD‑1–positive, Chymase‑negative mast cell phenotype links to metastatic melanoma and worse survival
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42912494
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42912494/)
- **DOI:** [10.1080/2162402X.2026.2752644](https://doi.org/10.1080%2F2162402X.2026.2752644)
- **Published At:** 2026-10-23T22:55:27.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- The investigators performed high-dimensional phenotyping of **mast cells** (MCs) after co-culture with melanoma spheroids, combined with trajectory inference and transcriptomic analyses to probe MC programs in melanoma. - Human melanoma tissues had similar overall MC abundance across outcome groups, but metastatic tumors were enriched for **Tryptase+ Chymase-** MCs compared with nonmetastatic samples. - Exposure to melanoma induced MC remodeling: loss of lineage- and effector-associated features and an increase in **PD‑1** expression; these changes were more marked after co-culture with metastatic melanoma. - Trajectory inference suggested a continuum of remodeling toward a **PD‑1+ Chymase-** phenotype; this phenotype was detected in melanoma tissues and concentrated in intratumoral regions of metastatic cases. - The study team translated experimentally observed protein changes into two transcriptomic signatures: an MC-lineage/effector-enriched signature (MC-LE) and a melanoma-remodeled signature (MC-MR), with opposing clinical associations. - Data indicated the **MC-LE** signature correlated with favorable survival and interferon-responsive pathways, while the **MC-MR** signature correlated with poorer survival and tumor-associated pathways. - These transcriptomic associations were observed across multiple TCGA cancer cohorts, extending beyond melanoma, and independent analyses of MCs from healthy skin, basal cell carcinoma, and melanoma showed corresponding MC-LE–related differences. - The abstract does not report sample sizes, specific marker panels, statistical values, or detailed methods for co-culture and transcriptomic generation; those methodological details were not provided in the source abstract.
## Clinical Analysis & Structured Key Points
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Epub 2026 Oct 23. # Mast cell phenotypic remodeling toward a PD-1-positive, Chymase-negative phenotype is associated with metastatic melanoma and poor survival [Julián A Gajón](https://pubmed.ncbi.nlm.nih.gov/?term=Gaj%C3%B3n+JA&cauthor_id=42912494)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42912494/#full-view-affiliation-1 "Unidad de Investigación Médica en Inmunología, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de México, México."), [Laura C Bonifaz](https://pubmed.ncbi.nlm.nih.gov/?term=Bonifaz+LC&cauthor_id=42912494)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42912494/#full-view-affiliation-2 "Coordinación de Investigación en Salud, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de México, México.")[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42912494/#full-view-affiliation-3 "Unidad de Investigación Médica en Inmunoquímica, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de México, México."), [Ezequiel Fuentes-Panana](https://pubmed.ncbi.nlm.nih.gov/?term=Fuentes-Panana+E&cauthor_id=42912494)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42912494/#full-view-affiliation-4 "Unidad de Investigación en Virología y Cáncer, Hospital Infantil de México Federico Gómez, Ciudad de México, México."), [Samira Muñoz-Cruz](https://pubmed.ncbi.nlm.nih.gov/?term=Mu%C3%B1oz-Cruz+S&cauthor_id=42912494)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42912494/#full-view-affiliation-3 "Unidad de Investigación Médica en Inmunoquímica, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de México, México.") Affiliations Expand ### Affiliations * 1 Unidad de Investigación Médica en Inmunología, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de México, México. * 2 Coordinación de Investigación en Salud, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de México, México. * 3 Unidad de Investigación Médica en Inmunoquímica, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de México, México. * 4 Unidad de Investigación en Virología y Cáncer, Hospital Infantil de México Federico Gómez, Ciudad de México, México. * PMID: **42912494** * DOI: [ 10.1080/2162402X.2026.2752644 ](https://doi.org/10.1080/2162402x.2026.2752644) Item in Clipboard # Mast cell phenotypic remodeling toward a PD-1-positive, Chymase-negative phenotype is associated with metastatic melanoma and poor survival Julián A Gajón et al. Oncoimmunology. 2026. Show details Display options Display options Format Abstract PubMed PMID Oncoimmunology Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Oncoimmunology%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Oncoimmunology%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42912494/) . 2026 Dec 31;15(1):2752644. doi: 10.1080/2162402X.2026.2752644. Epub 2026 Oct 23. ### Authors [Julián A Gajón](https://pubmed.ncbi.nlm.nih.gov/?term=Gaj%C3%B3n+JA&cauthor_id=42912494)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42912494/#short-view-affiliation-1 "Unidad de Investigación Médica en Inmunología, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de México, México."), [Laura C Bonifaz](https://pubmed.ncbi.nlm.nih.gov/?term=Bonifaz+LC&cauthor_id=42912494)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42912494/#short-view-affiliation-2 "Coordinación de Investigación en Salud, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de México, México.")[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42912494/#short-view-affiliation-3 "Unidad de Investigación Médica en Inmunoquímica, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de México, México."), [Ezequiel Fuentes-Panana](https://pubmed.ncbi.nlm.nih.gov/?term=Fuentes-Panana+E&cauthor_id=42912494)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42912494/#short-view-affiliation-4 "Unidad de Investigación en Virología y Cáncer, Hospital Infantil de México Federico Gómez, Ciudad de México, México."), [Samira Muñoz-Cruz](https://pubmed.ncbi.nlm.nih.gov/?term=Mu%C3%B1oz-Cruz+S&cauthor_id=42912494)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42912494/#short-view-affiliation-3 "Unidad de Investigación Médica en Inmunoquímica, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de México, México.") ### Affiliations * 1 Unidad de Investigación Médica en Inmunología, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de México, México. * 2 Coordinación de Investigación en Salud, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de México, México. * 3 Unidad de Investigación Médica en Inmunoquímica, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de México, México. * 4 Unidad de Investigación en Virología y Cáncer, Hospital Infantil de México Federico Gómez, Ciudad de México, México. * PMID: **42912494** * DOI: [ 10.1080/2162402X.2026.2752644 ](https://doi.org/10.1080/2162402x.2026.2752644) Item in Clipboard Cite Display options Display options Format Abstract PubMed PMID Linked Discoveries ## 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. **Keywords:** Mast cells; PD-1; mast cell plasticity; melanoma; tumor immunity; tumor microenvironment. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## MeSH terms * Cell Line, Tumor Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Cell+Line%2C+Tumor%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Cell+Line%2C+Tumor) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42912494/) * Chymases* / metabolism Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Chymases%2Fmetabolism%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Chymases) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42912494/) * Coculture Techniques Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Coculture+Techniques%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Coculture+Techniques) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42912494/) * Female Actions * [ Search in 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