title: IL15 can reverse the unresponsiveness of Wilms' tumor antigen-specific CTL in patients with prostate cancer.
abstract: OBJECTIVE
  The Wilms' tumor antigen 1 (WT1) is overexpressed in several leukemias and solid tumors, but there is currently limited information regarding its role in prostate cancer. This study aimed to investigate WT1 expression in prostate cancer, and to determine the number and function of WT1-specific T cells in the peripheral blood of patients.
  
  
  METHODS
  Immunohistochemistry was used to assess WT1 expression in cancer tissues. Human leukocyte antigen A2 (HLA-A2) tetramers served to detect WT1-specific T cells, and peptide-specific stimulation was used to assess T-cell function in vitro.
  
  
  RESULTS
  Immunohistochemistry of tissue arrays comprising 36 cancer and 8 normal prostate samples revealed nuclear WT1 staining in 39% of cancer samples, but not in normal prostate tissues. Tetramer analysis revealed a low frequency of WT1-specific T cells in 20 of 38 HLA-A2-positive patients. In vitro stimulation with WT1 peptide plus interleukin 2(IL2) and interleukin 7 (IL7) did not lead to an accumulation of WT1-specific T cells in any of the patient samples, although all patients were able to generate T-cell responses against Melan-A/MART1 control peptide. Stimulation with WT1 peptide in the presence of interleukin 15 (IL15), a cytokine that was shown to reverse tolerance of murine tumor-specific T cells, was able to restore the expansion and IFNgamma production of WT1-specific T cells in a subgroup of prostate cancer patients.
  
  
  CONCLUSIONS
  The observation that IL15 can restore the function of WT1-specific T cells that were unresponsive to IL2 has implications for vaccination and immunotherapeutic strategies that aim to enhance WT1-specific T cell immunity in patients.
authors.affiliation: Department of Immunology, University College London, Royal Free Hospital, London, United Kingdom.
authors.forename: Judy W
authors.initials: JW
authors.lastname: King
authors.forename: Sharyn
authors.initials: S
authors.lastname: Thomas
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Corsi
authors.forename: Liquan
authors.initials: L
authors.lastname: Gao
authors.forename: Roberto
authors.initials: R
authors.lastname: Dina
authors.forename: Roopinder
authors.initials: R
authors.lastname: Gillmore
authors.forename: Katharine
authors.initials: K
authors.lastname: Pigott
authors.forename: Amir
authors.initials: A
authors.lastname: Kaisary
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Stauss
authors.forename: Jonathan
authors.initials: J
authors.lastname: Waxman
mesh_terms: D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D015789:HLA-A2 Antigen / Q000502:physiology; D006801:Humans; D019409:Interleukin-15 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology; D015851:Interleukin-7 / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000276:immunology; D025721:WT1 Proteins / Q000032:analysis / Q000276:immunology*
chemical_list: D015789:HLA-A2 Antigen; D019409:Interleukin-15; D007376:Interleukin-2; D015851:Interleukin-7; D025721:WT1 Proteins