Expression of IL-27 by Tumor Cells in InvasCutaneous and Metastatic Melanomas

Interleukin (IL)-27 is a cytokine of the IL-12 family that displays either immunostimulatory or immunosuppressive functions depending on the context. In various murine tumor models including melanoma models, ectopic expression of IL-27 has been shown to play an anti-tumoral role and to favor tumor r...

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Bibliographic Details
Published in:PloS one 2013-10, Vol.8 (10), p.e75694
Main Authors: Gonin, Julie, Carlotti, Agnès, Dietrich, Céline, Audebourg, Anne, Radenen-Bussière, Brigitte, Caignard, Anne, Avril, Marie-Françoise, Vacher-Lavenu, Marie-Cécile, Larousserie, Frédérique, Devergne, Odile
Format: Article
Language:English
Subjects:
Analysis
Animal models
Cancer metastasis
Cytokines
Ectopic expression
Immunostimulation
Immunosuppression
Immunosuppressive agents
Interleukin 10
Interleukin 12
Interleukin 27
Interleukins
Lesions
Ligands
Lymphocytes
Lymphoma
Mathematical models
Melanoma
Metastases
Metastasis
Molecular chains
Nevus
PD-L1 protein
Regression analysis
Skin cancer
Studies
Tumor cells
Tumors
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Summary:Interleukin (IL)-27 is a cytokine of the IL-12 family that displays either immunostimulatory or immunosuppressive functions depending on the context. In various murine tumor models including melanoma models, ectopic expression of IL-27 has been shown to play an anti-tumoral role and to favor tumor regression. In this study, we investigated whether IL-27 might play a role in the development of melanoma in humans. We analyzed the in situ expression of IL-27 in melanocytic lesions (n = 82) representative of different stages of tumor progression. IL-27 expression was not observed in nevus (n = 8) nor in in situ melanoma (n = 9), but was detected in 28/46 (61%) cases of invasive cutaneous melanoma, notably in advanced stages (19/23 cases of stages 3 and 4). In most cases, the main source of IL-27 was tumor cells. Of note, when IL-27 was detected in primary cutaneous melanomas, its expression was maintained in metastatic lesions. These in situ data suggested that the immunosuppressive functions of IL-27 may dominate in human melanoma. Consistent with this hypothesis, we found that IL-27 could induce suppressive molecules such as PD-L1, and to a lesser extent IL-10, in melanoma cells, and that the in situ expression of IL-27 in melanoma correlated with those of PD-L1 and IL-10.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0075694