IL-27 induces the expression of IDO and PD-L1 in human cancer cells

IL-27 is a member of the IL-12 family that is produced by macrophages and dendritic cells. IL-27 inhibits the growth and invasiveness of different cancers and therefore represents a potential anti-tumor agent. By contrast, it may exert immune-regulatory properties in different biological systems. We...

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Main Authors:	Carbotti, Grazia, Barisione, Gaia, Airoldi, Irma, Mezzanzanica, Delia, Bagnoli, Marina, Ferrero, Simone, Petretto, Andrea, Fabbi, Marina, Ferrini, Silvano
Format:	Online
Language:	English
Published:	Impact Journals LLC 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4791231/

id	pubmed-4791231
recordtype	oai_dc
spelling	pubmed-47912312016-03-28 IL-27 induces the expression of IDO and PD-L1 in human cancer cells Carbotti, Grazia Barisione, Gaia Airoldi, Irma Mezzanzanica, Delia Bagnoli, Marina Ferrero, Simone Petretto, Andrea Fabbi, Marina Ferrini, Silvano Research Paper: Immunology IL-27 is a member of the IL-12 family that is produced by macrophages and dendritic cells. IL-27 inhibits the growth and invasiveness of different cancers and therefore represents a potential anti-tumor agent. By contrast, it may exert immune-regulatory properties in different biological systems. We reported that IL-27 induces the expression of the IL-18 inhibitor IL-18BP, in human Epithelial Ovarian Cancer (EOC) cells, thus potentially limiting the immune response. Here, we tested whether IL-27 may modulate other immune-regulatory molecules involved in EOC progression, including Indoleamine 2,3-dioxygenase (IDO) and Programmed Death-Ligand (PD-L)1. IDO and PD-L1 were not constitutively expressed by EOC cells in vitro, but IL-27 increased their expression through STAT1 and STAT3 tyrosine phosphorylation. Differently, cells isolated from EOC ascites showed constitutive activation of STAT1 and STAT3 and IDO expression. These findings, together with the expression of IL-27 in scattered leukocytes in EOC ascites and tissues, suggest a potential role of IL-27 in immune-regulatory networks of EOC. In addition, IL-27 induced IDO or PD-L1 expression in monocytes and in human PC3 prostate and A549 lung cancer cells. A current paradigm in tumor immunology is that tumor cells may escape from immune control due to “adaptive resistance” mediated by T cell-secreted IFN-γ, which induces PD-L1 and IDO expression in tumor cells. Our present data indicate that also IL-27 has similar activities and suggest that the therapeutic use of IL-27 as anti-cancer agent may have dual effects, in some tumors. Impact Journals LLC 2015-12-09 /pmc/articles/PMC4791231/ /pubmed/26657115 Text en Copyright: © 2015 Carbotti et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Carbotti, Grazia Barisione, Gaia Airoldi, Irma Mezzanzanica, Delia Bagnoli, Marina Ferrero, Simone Petretto, Andrea Fabbi, Marina Ferrini, Silvano
spellingShingle	Carbotti, Grazia Barisione, Gaia Airoldi, Irma Mezzanzanica, Delia Bagnoli, Marina Ferrero, Simone Petretto, Andrea Fabbi, Marina Ferrini, Silvano IL-27 induces the expression of IDO and PD-L1 in human cancer cells
author_facet	Carbotti, Grazia Barisione, Gaia Airoldi, Irma Mezzanzanica, Delia Bagnoli, Marina Ferrero, Simone Petretto, Andrea Fabbi, Marina Ferrini, Silvano
author_sort	Carbotti, Grazia
title	IL-27 induces the expression of IDO and PD-L1 in human cancer cells
title_short	IL-27 induces the expression of IDO and PD-L1 in human cancer cells
title_full	IL-27 induces the expression of IDO and PD-L1 in human cancer cells
title_fullStr	IL-27 induces the expression of IDO and PD-L1 in human cancer cells
title_full_unstemmed	IL-27 induces the expression of IDO and PD-L1 in human cancer cells
title_sort	il-27 induces the expression of ido and pd-l1 in human cancer cells
description	IL-27 is a member of the IL-12 family that is produced by macrophages and dendritic cells. IL-27 inhibits the growth and invasiveness of different cancers and therefore represents a potential anti-tumor agent. By contrast, it may exert immune-regulatory properties in different biological systems. We reported that IL-27 induces the expression of the IL-18 inhibitor IL-18BP, in human Epithelial Ovarian Cancer (EOC) cells, thus potentially limiting the immune response. Here, we tested whether IL-27 may modulate other immune-regulatory molecules involved in EOC progression, including Indoleamine 2,3-dioxygenase (IDO) and Programmed Death-Ligand (PD-L)1. IDO and PD-L1 were not constitutively expressed by EOC cells in vitro, but IL-27 increased their expression through STAT1 and STAT3 tyrosine phosphorylation. Differently, cells isolated from EOC ascites showed constitutive activation of STAT1 and STAT3 and IDO expression. These findings, together with the expression of IL-27 in scattered leukocytes in EOC ascites and tissues, suggest a potential role of IL-27 in immune-regulatory networks of EOC. In addition, IL-27 induced IDO or PD-L1 expression in monocytes and in human PC3 prostate and A549 lung cancer cells. A current paradigm in tumor immunology is that tumor cells may escape from immune control due to “adaptive resistance” mediated by T cell-secreted IFN-γ, which induces PD-L1 and IDO expression in tumor cells. Our present data indicate that also IL-27 has similar activities and suggest that the therapeutic use of IL-27 as anti-cancer agent may have dual effects, in some tumors.
publisher	Impact Journals LLC
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4791231/
_version_	1613551570682642432

IL-27 induces the expression of IDO and PD-L1 in human cancer cells

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