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

Grazia Carbotti, Gaia Barisione, Irma Airoldi, Delia Mezzanzanica, Marina Bagnoli, Simone Ferrero, Andrea Petretto, Marina Fabbi, Silvano Ferrini

Research output: Contribution to journalArticle

Abstract

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 immuneregulatory 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 (PDL) 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.

Original languageEnglish
Pages (from-to)43267-43280
Number of pages14
JournalOncotarget
Volume6
Issue number41
DOIs
Publication statusPublished - 2015

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Keywords

  • IDO
  • IL-27
  • Immune response
  • Immunity
  • Immunology and Microbiology Section
  • PD-L1
  • STAT

ASJC Scopus subject areas

  • Oncology

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