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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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Detalles Bibliográficos
Autores principales: Gonin, Julie, Carlotti, Agnès, Dietrich, Céline, Audebourg, Anne, Radenen-Bussière, Brigitte, Caignard, Anne, Avril, Marie-Françoise, Vacher-Lavenu, Marie-Cécile, Larousserie, Frédérique, Devergne, Odile
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3794994/
https://www.ncbi.nlm.nih.gov/pubmed/24130734
http://dx.doi.org/10.1371/journal.pone.0075694
Descripción
Sumario: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.