title: RETRACTED: Identification of an antitumor immune response of polyhistidine through a toll-like receptor 4-dependent manner.
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.
authors.affiliation: Department of Gastroenterology, The Tenth People's Hospital of Shanghai, Tongji University, Shanghai 200072, PR China; Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030, USA; Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA. Electronic address: yyang@houstonmethodist.org.
authors.forename: Yong
authors.initials: Y
authors.lastname: Yang
mesh_terms: D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D006639:Histidine / Q000276:immunology* / Q000494:pharmacology*; D007167:Immunotherapy; D008546:Melanoma, Experimental / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018625:Microscopy, Atomic Force; D055503:Protein Multimerization; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; C033223:polyhistidine; D006639:Histidine
keywords: Cancer immunotherapy; Polyhistidine; Single-molecule fluorescence imaging; Single-molecule force measurement; Toll-like receptor 4