title: Ustekinumab improves psoriasis without suppressing tumor antigen-specific cytotoxic T lymphocytes.
abstract: BACKGROUND
  Ustekinumab is currently used for the treatment of psoriasis with remarkable efficiency. However, worries about the development of malignancies in ustekinumab-treated patients have not been completely resolved because of the major role of IL-12 and IL-23 in tumor immunity. In the present study, we tried to elucidate the effects of ustekinumab on antigen-specific tumor immunity.
  
  
  METHODS
  After approval by the institutional ethical committee, a 56-year-old male volunteer with psoriasis was administered with 20 doses of WT1 peptide. WT1-specific cytotoxic T lymphocytes (CTLs) were evaluated by WT1 tetramer assay after mixed lymphocyte peptide culture.
  
  
  RESULTS
  WT1 tetramer+ T cells with cytotoxic ability appeared in the blood after peptide administration and the frequency of WT1 tetramer+ T cells increased to more than 15 in 10(6) CD8+ T cells. Thirty months after stopping WT1 administration, the patient commenced treatment with ustekinumab for psoriasis at weeks 0 and 4, and every 12 weeks thereafter. Psoriasis plaques were almost cleared up and the response to ustekinumab has so far lasted for 30 months. The frequency of WT1 tetramer+ T cells has not changed since the initiation of ustekinumab treatment. The effects of ustekinumab on the antigen-presenting and CTL-inducing abilities of dendritic cells were explored in vitro, revealing limited effects on both immune functions.
  
  
  CONCLUSIONS
  These in vivo/vitro findings imply that ustekinumab improves psoriasis without suppressing tumor antigen-specific CTLs and support the data of recent clinical trials showing no increased incidence of malignancies with ustekinumab treatment.
authors.affiliation: Laboratory of Hematology and Oncology, Graduate School of Health Sciences, Niigata University, Niigata, Japan.
authors.forename: Miwako
authors.initials: M
authors.lastname: Narita
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Nishizawa
authors.forename: Shunpei
authors.initials: S
authors.lastname: Iwaya
authors.forename: Eri
authors.initials: E
authors.lastname: Oiwa
authors.forename: Minami
authors.initials: M
authors.lastname: Iwabuchi
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Uchiyama
authors.forename: Asako
authors.initials: A
authors.lastname: Matsuyama
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Masuko
authors.forename: Masuhiro
authors.initials: M
authors.lastname: Takahashi
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D006801:Humans; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology*; D000069549:Ustekinumab; D025721:WT1 Proteins / Q000097:blood / Q000276:immunology
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D025721:WT1 Proteins; C583751:WT1 protein, human; D000069549:Ustekinumab