ArticleJournal for immunotherapy of cancer2024
Digital spatial proteomic profiling reveals immune checkpoints as biomarkers in lymphoid aggregates and tumor microenvironment of desmoplastic melanoma.
Article in Journal for immunotherapy of cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 11 citations in OpenAlex.
- Development of functional spatial mapping of the tumour immune microenvironment (FuncO:TiME) in advanced melanomas.BJC reports · 2026Article
- YAP-activated lymph node fibroblasts contribute to extracellular matrix remodeling associated with extranodal extension of oral squamous cell carcinoma.The journal of pathology. Clinical research · 2026Article
- Clinical impact and therapeutic potential of tertiary lymphoid structures in melanoma.Frontiers in immunology · 2026Review
- Modeling rare melanoma subtypes: mechanisms, microenvironments and translational opportunities.Frontiers in oncology · 2026Review
- Exploring tumor heterogeneity and drug resistance in cervical cancer through single-cell and bulk transcriptomics.Discover oncology · 2025Article
- Pathomic immune biomarkers define recurrence risk in early-stage melanoma.The oncologist · 2025Article
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- Next-generation sequencing impact on cancer care: applications, challenges, and future directions.Frontiers in genetics · 2024Review
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundDesmoplastic melanoma (DM) is a rare melanoma subtype characterized by dense fibrous stroma, a propensity for local recurrence, and a high response rate to programmed cell death protein 1 (PD-1) blockade. Occult sentinel lymph node positivity is significantly lower in both pure and mixed DM than in conventional melanoma, underscoring the need for better prognostic biomarkers to inform therapeutic strategies.
methodsWe assembled a tissue microarray comprising various cores of tumor, stroma, and lymphoid aggregates from 45 patients with histologically confirmed DM diagnosed between 1989 and 2018. Using a panel of 62 validated immune-oncology markers, we performed digital spatial profiling using the NanoString GeoMx platform and quantified expression in three tissue compartments defined by fluorescence colocalization (tumor (S100+/PMEL+/SYTO+), leukocytes (CD45+/SYTO+), and non-immune stroma (S100-/PMEL-/CD45-/SYTO+)).
resultsWe observed higher expression of immune checkpoints (lymphocyte-activation gene 3 [LAG-3] and cytotoxic T-lymphocyte associated protein-4 [CTLA-4]) and cancer-associated fibroblast (CAF) markers (smooth muscle actin (SMA)) in the tumor compartments of pure DMs than mixed DMs. When comparing lymphoid aggregates (LA) to non-LA tumor cores, LAs were more enriched with CD20+B cells, but non-LA intratumoral leukocytes were more enriched with macrophage/monocytic markers (CD163, CD68, CD14) and had higher LAG-3 and CTLA-4 expression levels. Higher intratumoral PD-1 and LA-based LAG-3 expression appear to be associated with worse survival.
conclusionsOur proteomic analysis reveals an intra-tumoral population of SMA+CAFs enriched in pure DM. Additionally, increased expressions of immune checkpoints (LAG-3 and PD-1) in LA and within tumor were associated with poorer prognosis. These findings might have therapeutic implications and help guide treatment selection in addition to informing potential prognostic significance.
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