PD-1 expression on Melan-A-reactive T cells increases during progression to metastatic disease
Programmed death 1 (PD‐1) is known as an important factor for the development of tolerogenicity. This has been proven in chronic viral infections and different tumor models. To address the role of PD‐1 and its ligand programmed death ligand 1 (PD‐L1) in different stages of malignant melanoma, we inv...
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Published in | International journal of cancer Vol. 130; no. 10; pp. 2327 - 2336 |
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Main Authors | , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Hoboken
Wiley Subscription Services, Inc., A Wiley Company
15.05.2012
Wiley-Blackwell Wiley Subscription Services, Inc |
Subjects | |
Online Access | Get full text |
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Summary: | Programmed death 1 (PD‐1) is known as an important factor for the development of tolerogenicity. This has been proven in chronic viral infections and different tumor models. To address the role of PD‐1 and its ligand programmed death ligand 1 (PD‐L1) in different stages of malignant melanoma, we investigated peripheral blood and tumor tissues in regard to overall survival (OS) and prognostic relevance. One hundred samples of peripheral blood mononuclear cells from HLA‐A2+ patients with malignant melanoma (Stages I–IV) were analyzed in seven color FACS combined with multimer analyses for the immunodominant epitope of Melan‐A (peptide A2/Melan‐Ap26‐35mod). Corresponding formalin‐fixed paraffin‐embedded tissues of primary tumor and distant organ metastases from 37 cases were analyzed by immunohistochemistry for Melan‐A, PD‐L1 and PD‐1 expression. Compared to the total CD8+ T cell population, PD‐1 expression by A2/Melan‐A+ CD8+ T cells was over‐represented in melanoma stages III and IV (p < 0.001). Although elevation of PD‐1+ Melan‐A+ CD8+ T cells had no significant influence on OS, a positive correlation was observed between PD‐L1 expression on melanoma cells and OS (p = 0.05). Correlation of advanced tumor stage with increased A2/Melan‐A‐multimer+ PD‐1+ T cells in the peripheral blood suggest that blocking of PD‐1 could have therapeutic potential in advanced stage melanoma. |
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Bibliography: | istex:B6EF96D7F62397898DDC61F3CD776C0F9EB7A810 ArticleID:IJC26272 Helmholtz Alliance (Immunotherapy of Cancer) This article was published online on 11 January 2012. An error was subsequently identified. This notice is included in the online and print versions to indicate that both have been corrected on 9th February 2012. ark:/67375/WNG-8X2SVJ3Q-K Research Council of Germany - No. SFB 456; No. DFG BE 1579/4-1 Tel.: +49‐89‐4140‐6223, Fax: +49‐89‐4140‐4854 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0020-7136 1097-0215 |
DOI: | 10.1002/ijc.26272 |