ArticleTranslational cancer research2025
Identification of the immune subtypes associated with the prognosis and immunotherapy of metastatic melanoma.
Article in Translational cancer research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Melanoma is an aggressive malignant tumor, characterized by high mortality. A growing amount of research indicates that the tumor immune microenvironment is closely associated with the survival outcomes and immunotherapy benefit for patients with advanced tumors. However, the molecular mechanisms underlying the effect of the tumor immune microenvironment on metastatic melanoma have not been clarified in detail. Therefore, this study aimed to identify potential effective immune-related tumor biomarkers for the prognosis and treatment of metastatic melanoma. Methods: Consensus clustering analysis was performed to identify robust clusters of metastatic melanoma in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) based on the nCounter immune gene expression profiles (NanoString). We used Estimation of Stromal and Immune Cells in Malignant Tumor Tissues Using Expression Data (ESTIMATE) and Cell-type Identification by Estimating Relative Subsets of Known RNA Transcripts (CIBERSORT) to study the microenvironment of different subtypes. Additionally, we constructed a prognostic model via binomial logistic regression analysis, and used an anti-programmed cell death 1 (anti-PD-1) immunotherapy cohort to validate the subtypes. Results: Two immune-associated clusters were identified in metastatic melanoma, with the immune-high subtype demonstrating a better clinical outcome than the Immune-Low subtype. Compared with the Immune-Low subtype, the immune-high subtype exhibited a significantly higher immune and stromal score, along with greater proportions of naïve B cells, plasma cells, CD8 T cells, memory activated CD4 T cells, activated natural killer (NK) cells, and M1 macrophages. Meanwhile, the proportion of resting NK cells, M0 macrophages, M2 macrophages, resting mast cells, and eosinophils were greater in the Immune-Low subtype. Elevated expressions of human leukocyte antigen (HLA) genes, immune checkpoint molecules, and T-cell receptor repertoire diversity were also observed in the Immune-High subtype, while the frequency of copy number variants was higher in the Immune-Low subtype. Furthermore, we constructed a 36-gene prognostic model, and the Immune-High subtype exhibited more benefit to immunotherapy. Conclusions: Our immune-associated model may have clinical implications for the prognosis and treatment guidance in patients with metastatic melanoma.
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