PD-1 expression on Melan-A-reactive T cells increases during progression to metastatic disease

• Published in: International journal of cancer Vol. 130; no. 10; pp. 2327 - 2336
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 15.05.2012; Wiley-Blackwell; Wiley Subscription Services, Inc
• Subjects: A2/Melan-A; Aged; B7-H1; B7-H1 Antigen - metabolism; Biological and medical sciences; Cancer; CD8-Positive T-Lymphocytes - metabolism; Dermatology; Disease Progression; Female; Humans; Ligands; Lymphocytes; Lymphocytes, Tumor-Infiltrating - immunology; Male; malignant melanoma; MART-1 Antigen - metabolism; Medical research; Medical sciences; Melanoma; Melanoma - immunology; Melanoma - mortality; Melanoma - secondary; Middle Aged; PD-1; PD-L1; Programmed Cell Death 1 Receptor - metabolism; Skin cancer; Skin Neoplasms - immunology; Skin Neoplasms - mortality; Skin Neoplasms - pathology; T cell receptors; Tumors; Tumors of the skin and soft tissue. Premalignant lesions; A2/Melan-A; Programmed cell death protein 1; Malignant tumor; Metastasis; Costimulatory molecule; Cancerology; T-Lymphocyte; Malignant melanoma; PD-L1; Advanced stage; B7-H1; Cell adhesion molecule L1; PD-1; Cancer; B7-H1 molecule
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.26272

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.