title: Expression of IL-27 by tumor cells in invasive cutaneous and metastatic melanomas [corrected]..
abstract: 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.
authors.affiliation: Centre National de la Recherche Scientifique Unité Mixte de Recherche 8147, Université Paris Descartes, Sorbonne Paris Cité, Paris, France ; Service d'Anatomie Pathologique and Université Paris Descartes, Assistance Publique des Hôpitaux de Paris, Hôpital Cochin, Paris, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Gonin
authors.forename: Agnès
authors.initials: A
authors.lastname: Carlotti
authors.forename: Céline
authors.initials: C
authors.lastname: Dietrich
authors.forename: Anne
authors.initials: A
authors.lastname: Audebourg
authors.forename: Brigitte
authors.initials: B
authors.lastname: Radenen-Bussière
authors.forename: Anne
authors.initials: A
authors.lastname: Caignard
authors.forename: Marie-Françoise
authors.initials: MF
authors.lastname: Avril
authors.forename: Marie-Cécile
authors.initials: MC
authors.lastname: Vacher-Lavenu
authors.forename: Frédérique
authors.initials: F
authors.lastname: Larousserie
authors.forename: Odile
authors.initials: O
authors.lastname: Devergne
mesh_terms: D060890:B7-H1 Antigen / Q000378:metabolism; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D016753:Interleukin-10 / Q000378:metabolism; D064094:Interleukin-27 / Q000378:metabolism* / Q000494:pharmacology; D008545:Melanoma / Q000378:metabolism*; D009508:Nevus, Pigmented / Q000378:metabolism*; D012878:Skin Neoplasms; D000096142:Cutaneous Malignant Melanoma
chemical_list: D060890:B7-H1 Antigen; C423236:CD274 protein, human; D064094:Interleukin-27; D016753:Interleukin-10