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A 3D Organotypic Melanoma Spheroid Skin Model
Published on: May 18, 2018
Overall survival and PD-L1 expression in metastasized malignant melanoma
Jules Gadiot1, Anna I Hooijkaas, Andrew D M Kaiser
1Division of Immunology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital (NKI-AVL), Amsterdam, The Netherlands.
Background:
Cancers are known to elude the immune system, for example, by MHC loss, FAS up-regulation, or increased secretion of TGF-beta. Recently, ligands of coinhibitory receptors like programmed cell death ligand-1 (PD-L1, B7-H1) have come to attention for their role in tumor immune escape. Various tumors have been tested for PD-L1 expression, and conflicting results were obtained regarding its correlative impact on patient survival. This study aimed to determine the prognostic relevance of PD-L1 expression for the survival of melanoma patients.
Methods:
Paraffin-embedded nevi, primary melanoma, and in-transit, lymph node, and distant organ metastases from a set of 63 stages III-IV melanoma patients referred to the Netherlands Cancer Institute between 2000 and 2004 for a sentinel-node procedure or systemic therapy were studied. A large effort was invested in validating specific PD-L1 staining. In addition to immunological factors such as T-cell infiltration (CD8, CD4, and regulatory T cells), TGF-beta and MHC-I expression were assessed.
Results:
Longitudinal analysis revealed no relevant PD-L1 expression on primary melanoma compared with metastatic disease. No significant correlations with prognosis were found regarding immunological factors, whereas known prognostic markers such as Breslow thickness and sex could be confirmed. Analyses of the overall survival of our patient cohort did not reveal a negative association with PD-L1 expression.
Conclusions:
Correlation of overall survival with PD-L1 expression by melanoma cells remains controversial, and future clinical studies should focus on antibody validation and time of analysis in respect to disease progression.
Insights
Programmed cell death ligand-1 (PD-L1) expression in melanoma did not correlate with patient survival. Further studies are needed to validate antibodies and timing of analysis for PD-L1 in melanoma prognosis.
Area of Science:
- Oncology
- Immunology
- Dermatology
Background:
- Cancer cells evade immune surveillance through mechanisms like MHC loss and TGF-beta secretion.
- Programmed cell death ligand-1 (PD-L1) is implicated in tumor immune escape, but its prognostic value in melanoma is debated.
- Previous studies on PD-L1 expression in various tumors yielded conflicting survival correlation results.
Purpose of the Study:
- To investigate the prognostic relevance of PD-L1 expression in melanoma patients.
- To determine if PD-L1 expression correlates with overall survival in stages III-IV melanoma.
- To assess PD-L1 expression in primary and metastatic melanoma lesions.
Main Methods:
- Studied 63 stages III-IV melanoma patients' samples (nevi, primary, and metastatic lesions).
- Validated PD-L1 staining and assessed T-cell infiltration (CD8, CD4, Tregs), TGF-beta, and MHC-I expression.
- Performed longitudinal analysis and correlated findings with known prognostic markers like Breslow thickness and sex.
Main Results:
- No significant difference in PD-L1 expression between primary and metastatic melanoma was observed.
- Immunological factors showed no significant correlation with prognosis.
- Overall survival analysis did not reveal a negative association with PD-L1 expression in this patient cohort.
Conclusions:
- The correlation between PD-L1 expression on melanoma cells and overall survival remains controversial.
- Future clinical studies should prioritize antibody validation and the timing of PD-L1 analysis relative to disease progression.
- Further research is essential to clarify the role of PD-L1 in melanoma patient outcomes.
