Apigenin inhibits the inducible expression of programmed death ligand 1 by human and mouse mammary carcinoma cells

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102 Citations (Scopus)

Résumé

Programmed death ligand 1 (PD-L1) is expressed by many cancer cell types, as well as by activated T cells and antigen-presenting cells. Constitutive and inducible PD-L1 expression contributes to immune evasion by breast cancer (BC) cells. We show here that the dietary phytochemical apigenin inhibited interferon (IFN)-γ-induced PD-L1 upregulation by triple-negative MDA-MB-468 BC cells, HER2+ SK-BR-3 BC cells, and 4T1 mouse mammary carcinoma cells, as well as human mammary epithelial cells, but did not affect constitutive PD-L1 expression by triple-negative MDA-MB-231 BC cells. IFN-β-induced expression of PD-L1 by MDA-MB-468 cells was also inhibited by apigenin. In addition, luteolin, the major metabolite of apigenin, inhibited IFN-γ-induced PD-L1 expression by MDA-MB-468 cells. Apigenin-mediated inhibition of IFN-γ-induced PD-L1 expression by MDA-MB-468 and 4T1 cells was associated with reduced phosphorylation of STAT1, which was early and transient at Tyr701 and sustained at Ser727. Apigenin-mediated inhibition of IFN-γ-induced PD-L1 expression by MDA-MB-468 cells also increased proliferation and interleukin-2 synthesis by PD-1-expressing Jurkat T cells that were co-cultured with MDA-MB-468 cells. Apigenin therefore has the potential to increase the vulnerability of BC cells to T cell-mediated anti-tumor immune responses.

Langue d'origineEnglish
Pages (de-à)424-433
Nombre de pages10
JournalCancer Letters
Volume380
Numéro de publication2
DOI
Statut de publicationPublished - oct. 1 2016

Note bibliographique

Funding Information:
This work was supported by the Dalhousie Medical Research Foundation and the Canadian Breast Cancer Foundation-Atlantic Region . M. Harrison was the recipient of a Frederick Banting and Charles Best Canada Graduate Scholarship, a Canadian Imperial Bank of Commerce Graduate Scholarship in Medical Research and a Trainee Award from The Beatrice Hunter Cancer Research Institute as part of the Terry Fox Strategic Health Research Training Program in Cancer Research at the Canadian Institutes of Health Research.

Publisher Copyright:
© 2016 Elsevier Ireland Ltd

ASJC Scopus Subject Areas

  • Oncology
  • Cancer Research

PubMed: MeSH publication types

  • Journal Article

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