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Updated: Aug 7, 2025
A Melanoma Patient-Derived Xenograft Model
Published on: May 20, 2019
Nidogen-2 (NID2) is a Key Factor in Collagen Causing Poor Response to Immunotherapy in Melanoma
Yan Sha1, An-Qi Mao1, Yuan-Jie Liu2
1Departments of Dermatology, Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Zhangjiagang, People's Republic of China.
Background:
The incidence of cutaneous melanoma continues to rise rapidly and has an extremely poor prognosis. Immunotherapy strategies are the most effective approach for patients who have developed metastases, but not all cases have been successful due to the complex and variable mechanisms of melanoma response to immune checkpoint inhibition.
Methods:
We synthesized collagen-coding gene expression data (second-generation and single-cell sequencing) from public Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Bioinformatics analysis was performed using R software and several database resources such as Metascape database, Gene Set Cancer Analysis (GSCA) database, and Cytoscape software, etc., to investigate the biological mechanisms that may be related with collagens. Immunofluorescence and immunohistochemical staining were used to validate the expression and localization of Nidogen-2 (NID2).
Results:
Melanoma patients can be divided into two collagen clusters. Patients with high collagen levels (C1) had a shorter survival than those with low collagen levels (C2) and were less likely to benefit from immunotherapy. We demonstrated that NID2 is a potential key factor in the collagen phenotype, is involved in fibroblast activation in melanoma, and forms a barrier to limit the proximity of CD8+ T cells to tumor cells.
Conclusion:
We clarified the adverse effects of collagen on melanoma patients and identified NID2 as a potential therapeutic target.
Insights
High collagen levels in melanoma patients correlate with shorter survival and reduced immunotherapy benefit. Nidogen-2 (NID2) is identified as a key factor in this collagen phenotype, potentially offering a new therapeutic target for melanoma.
Area of Science:
- Oncology
- Immunology
- Genomics
Background:
- Cutaneous melanoma incidence is rising, with poor prognosis for metastatic cases.
- Immunotherapy is effective for metastases, but response varies due to complex mechanisms.
- Understanding melanoma's response to immune checkpoint inhibition is crucial.
Purpose of the Study:
- To investigate biological mechanisms related to collagens in melanoma.
- To identify key factors influencing melanoma's collagen phenotype.
- To explore potential therapeutic targets for melanoma.
Main Methods:
- Synthesized collagen-coding gene expression data from public databases (GEO, TCGA).
- Performed bioinformatics analysis using R, Metascape, GSCA, and Cytoscape.
- Validated Nidogen-2 (NID2) expression and localization via immunofluorescence and immunohistochemistry.
Main Results:
- Melanoma patients were divided into high (C1) and low (C2) collagen expression clusters.
- High collagen levels (C1) were associated with shorter survival and less immunotherapy benefit.
- Nidogen-2 (NID2) was identified as a key factor in the collagen phenotype, involved in fibroblast activation and limiting CD8+ T cell proximity.
Conclusions:
- Clarified the adverse effects of collagen on melanoma patient outcomes.
- Identified Nidogen-2 (NID2) as a potential therapeutic target for melanoma.
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