Stat3 inhibitor abrogates the expression of PD-1 ligands on lymphoma cell lines

J Clin Exp Hematop. 2017 Jul 5;57(1):21-25. doi: 10.3960/jslrt.17006. Epub 2017 May 10.

Abstract

Recent studies have indicated the significance of immune checkpoint molecules including programmed death-1 (PD-1), cytotoxic T-lymphocyte associated protein 4, and T-cell immunoglobulin and mucin domain-containing molecule-3 for anti-tumor immune responses. We previously investigated PD-1 ligand 1/2 (PD-L1/2) expression in lymphoma cell lines, and found that PD-L1/2 is expressed on the adult T-cell leukemia/lymphoma (ATL-T) and B-cell lymphoma (SLVL) cell lines. In the present study, we investigated whether the Stat3 inhibitor WP1066 abrogated PD-L1/2 expression in lymphoma cell lines. Incubation with WP1066 inhibited lymphoma cell growth and induced cell apoptosis. PD-L1/2 expression in the ATL-T, SLVL, and human brain malignant lymphoma (HKBML) cell lines was significantly abrogated by WP1066 treatment. These data indicated that a Stat3 inhibitor abrogated PD-L1/2 expression in lymphoma cells. Such an inhibitor is therefore considered to be useful for additional immunotherapy in patients with advanced lymphoma.

Keywords: PD-L1; PD-L2; Stat3; lymphoma.

MeSH terms

  • Apoptosis / drug effects
  • Apoptosis / genetics
  • B7-H1 Antigen / genetics*
  • Caspase 3 / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Lymphoma / genetics*
  • Lymphoma / metabolism
  • Pyridines / pharmacology
  • STAT3 Transcription Factor / antagonists & inhibitors*
  • Tyrphostins / pharmacology

Substances

  • B7-H1 Antigen
  • Pyridines
  • STAT3 Transcription Factor
  • Tyrphostins
  • WP1066
  • Caspase 3