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PD‐1 expression on Melan‐A‐reactive T cells increases during progression to metastatic disease
Author(s) -
Krönig Holger,
Julia Falchner Kathrin,
Odendahl Marcus,
Brackertz Bettina,
Conrad Heinke,
Muck Dieter,
Hein Rüdiger,
Blank Christian,
Peschel Christian,
Haller Bernhard,
Schulz Stephan,
Bernhard Helga
Publication year - 2012
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.26272
Subject(s) - melanoma , cd8 , medicine , peripheral blood mononuclear cell , epitope , immunohistochemistry , population , immunotherapy , pd l1 , cancer research , immunology , immune system , antigen , pathology , biology , in vitro , biochemistry , environmental health
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‐A p26‐35mod ). 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.