Interleukin-27 re-educates intratumoral myeloid cells and down-regulates stemness genes in non-small cell lung cancer

Irma Airoldi, Maria Grazia Tupone, Silvia Esposito, Marco V. Russo, Giulia Barbarito, Giuseppe Cipollone, Emma Di Carlo

Research output: Contribution to journalArticle

Abstract

Current therapies for Non-Small Cell Lung Cancer (NSCLC) still fail to significantly increase its survival rate. Here we asked whether Interleukin(IL)-27, which has revealed powerful antitumor activity and is toxicity-free in humans, is a promising therapeutic choice for NSCLC patients. IL-27's effects were tested on Adenocarcinoma (AC) and Squamous Cell Carcinoma (SCC) cell lines and xenograft models. IL-27Receptor(R) expression was assessed in lung tissues from 78 NSCLC patients. In vitro, IL-27 was ineffective on cancer cell proliferation or apoptosis, but fostered CXCL3/GROγ/MIP2β expression. In vitro and in vivo, IL-27 down-regulated stemness-related genes, namely SONIC HEDGEHOG in AC cells, and OCT4A, SOX2, NOTCH1, KLF4 along with Nestin, SNAI1/SNAIL, SNAI2/SLUG and ZEB1, in SCC cells. In vivo, IL-27 hampered both AC and SCC tumor growth in association with a prominent granulocyte- and macrophage-driven colliquative necrosis, CXCL3 production, and a reduced pluripotency- and EMT-related gene expression. Myeloablation of tumorbearing hosts mostly abolished IL-27's antitumor effects. In clinical samples, IL-27R expression was found in AC, SCC, pre-cancerous lesions and tumor infiltrating myeloid cells, and correlated with advanced stages of disease. Our data suggest that even immunocompromised or advancer NSCLC patients may benefit from IL-27's antitumor properties based on its ability to drive myeloid cells towards antitumor activities, and down-regulate stemness- and EMT-related genes in cancer cells.

Original languageEnglish
Pages (from-to)3694-3708
Number of pages15
JournalOncotarget
Volume6
Issue number6
Publication statusPublished - 2015

Keywords

  • Cytokines
  • Immunotherapy
  • Inflammation
  • Lung cancer
  • Tumor microenvironment

ASJC Scopus subject areas

  • Oncology

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  • Cite this

    Airoldi, I., Tupone, M. G., Esposito, S., Russo, M. V., Barbarito, G., Cipollone, G., & Di Carlo, E. (2015). Interleukin-27 re-educates intratumoral myeloid cells and down-regulates stemness genes in non-small cell lung cancer. Oncotarget, 6(6), 3694-3708.