The second and third authors contributed equally to this article.
Overall survival and PD-L1 expression in metastasized malignant melanoma
Article first published online: 29 NOV 2010
Copyright © 2010 American Cancer Society
Volume 117, Issue 10, pages 2192–2201, 15 May 2011
How to Cite
Gadiot, J., Hooijkaas, A. I., Kaiser, A. D. M., van Tinteren, H., van Boven, H. and Blank, C. (2011), Overall survival and PD-L1 expression in metastasized malignant melanoma. Cancer, 117: 2192–2201. doi: 10.1002/cncr.25747
- Issue published online: 26 APR 2011
- Article first published online: 29 NOV 2010
- Manuscript Accepted: 29 SEP 2010
- Manuscript Revised: 27 SEP 2010
- Manuscript Received: 16 AUG 2010
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.
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.
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.
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. Cancer 2011. © 2010 American Cancer Society.