Tilorone activates NK cells and cytotoxic lymphocytes that kill HLA-negative tumor cells

IUBMB Life. 2019 Mar;71(3):376-384. doi: 10.1002/iub.1985. Epub 2018 Dec 11.

Abstract

Tilorone hydrochloride, a low-molecular-weight synthetic compound, induces interferon production and has been reported to have both antiviral and antitumor activities. Here, we have demonstrated the ability of tilorone to activate NK cells and specific subpopulations of cytotoxic CD4+ and CD8+ T lymphocytes that recognize immune-evasive tumor cells and kill them via the FasL-Fas interaction. We have also performed a comparative analysis of characteristics between lymphocytes activated in the fraction of human peripheral blood mononuclear cells (PBMCs) upon treatment with different stimulants of the immune response: tilorone, innate immunity protein Tag7, and cytokine IL-2, a regulator of adaptive immunity. The results show that all the three stimulants, regardless of their nature, activate lymphocytes that are identical with respect to the spectrum of target cells, phenotype, and mechanism of cytotoxic action However, these stimulants induce different mechanisms of lymphocyte activation at early stages of the immune response. © 2018 IUBMB Life, 71(3):376-384, 2019.

Keywords: Fas; FasL; HLA-negative tumor cells; NK cells; Tag7; cytotoxic CD8+ T lymphocytes; tilorone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Cell Line
  • Coculture Techniques
  • Culture Media, Conditioned / pharmacology
  • Cytokines / pharmacology
  • Cytotoxicity, Immunologic / drug effects
  • Fas Ligand Protein / genetics
  • Fas Ligand Protein / immunology
  • Fibroblasts / cytology
  • Fibroblasts / drug effects
  • Fibroblasts / immunology
  • Gene Expression Regulation, Leukemic*
  • HeLa Cells
  • Humans
  • Immunity, Innate / drug effects
  • Interleukin-2 / pharmacology
  • K562 Cells
  • Killer Cells, Natural / cytology
  • Killer Cells, Natural / drug effects*
  • Killer Cells, Natural / immunology
  • Lymphocyte Activation / drug effects*
  • Mice
  • Primary Cell Culture
  • T-Lymphocytes, Cytotoxic / cytology
  • T-Lymphocytes, Cytotoxic / drug effects*
  • T-Lymphocytes, Cytotoxic / immunology
  • Tilorone / pharmacology*
  • fas Receptor / genetics
  • fas Receptor / immunology

Substances

  • Antineoplastic Agents
  • Culture Media, Conditioned
  • Cytokines
  • FAS protein, human
  • FASLG protein, human
  • Fas Ligand Protein
  • IL2 protein, human
  • Interleukin-2
  • PGLYRP1 protein, human
  • fas Receptor
  • Tilorone