RETRACTED: Identification of an antitumor immune response of polyhistidine through a toll-like receptor 4-dependent manner

Biochem Biophys Res Commun. 2014 Oct 10;453(1):148-52. doi: 10.1016/j.bbrc.2014.09.078. Epub 2014 Sep 26.

Abstract

Polyhistidine is widely used for the delivery of nucleic acids and antibodies into the cell cytoplasm. However, little attention has been concerned on the effect of polyhistidine on the immune system. In this work, we identify a novel function of polyhistidine as an activator of the immune system. Single-molecule fluorescence imaging and single-molecule force measurements show that polyhistidine binds specifically to the toll-like receptor 4 (TLR4), inducing receptor dimerization and activation. Moreover, in a B16 melanoma model we demonstrate that polyhistidine treatment inhibits tumor growth in TLR4(+/+) but not TLR4(-/-) mice. These results suggest the potential use of polyhistidine for cancer immunotherapy.

Keywords: Cancer immunotherapy; Polyhistidine; Single-molecule fluorescence imaging; Single-molecule force measurement; Toll-like receptor 4.

Publication types

  • Research Support, Non-U.S. Gov't
  • Retracted Publication

MeSH terms

  • Animals
  • Cytokines / genetics
  • Cytokines / metabolism
  • Histidine / immunology*
  • Histidine / pharmacology*
  • Immunotherapy
  • Melanoma, Experimental / immunology*
  • Melanoma, Experimental / pathology
  • Melanoma, Experimental / therapy*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microscopy, Atomic Force
  • Protein Multimerization
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism
  • Toll-Like Receptor 4 / deficiency
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / metabolism*

Substances

  • Cytokines
  • RNA, Messenger
  • RNA, Neoplasm
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4
  • polyhistidine
  • Histidine