title: Intravaginal and subcutaneous immunization induced vaccine specific CD8 T cells and tumor regression in the bladder.
abstract: OBJECTIVE
  Vaccines targeting tumor associated antigens are in development for bladder cancer. Most of these cancers are nonmuscle invasive at diagnosis and confined in the mucosa and submucosa. However, to our knowledge how vaccination may induce the regression of tumors at such mucosal sites has not been examined previously. We compared different immunization routes for the ability to induce vaccine specific antitumor CD8 T cells in the bladder and bladder tumor regression in mice.
  
  
  METHODS
  In the absence of a murine bladder tumor model expressing a tumor antigen relevant for human use we established an orthotopic model expressing the HPV-16 tumor antigen E7 as a model. We used an adjuvant E7 polypeptide to induce CD8 T cell mediated tumor regression.
  
  
  RESULTS
  Subcutaneous and intravaginal but not intranasal vaccination induced a high number of TetE7(+)CD8(+) T cells in the bladder as well as bladder tumor regression. The entry of vaccine specific T cells in the bladder was not the only key since persistent regression of established bladder tumors by intravaginal or subcutaneous immunization was associated with tumor infiltration of total CD4 and CD8 T cells. This resulted in an increase in TetE7(+)CD8(+) T cells and a decrease in T regulatory cells, leading to an increased number of effector interferon-γ secreting vaccine specific CD8 T cells in the regressing bladder tumor.
  
  
  CONCLUSIONS
  These data show that immunization routes should be tailored to each mucosal tumor site. Subcutaneous or intravaginal vaccination may be of additional value to treat patients with bladder cancer.
authors: Department of Urology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors: Sonia
authors: S
authors: Domingos-Pereira
authors: Department of Urology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors: Laurent
authors: L
authors: Derré
authors: Department of Urology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors: Loane
authors: L
authors: Warpelin-Decrausaz
authors: Department of Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors: Jacques-Antoine
authors: JA
authors: Haefliger
authors: Ludwig Center for Cancer Research of University of Lausanne, University of Lausanne, Lausanne, Switzerland.
authors: Pedro
authors: P
authors: Romero
authors: Department of Urology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors: Patrice
authors: P
authors: Jichlinski
authors: Department of Urology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. Electronic address: dnardell@hospvd.ch.
authors: Denise
authors: D
authors: Nardelli-Haefliger
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D005260:Female; D007114:Immunization; D051379:Mice; D050725:Papillomavirus E7 Proteins; D053918:Papillomavirus Vaccines / Q000276:immunology*; D001743:Urinary Bladder / Q000276:immunology*; D001749:Urinary Bladder Neoplasms / Q000276:immunology* / Q000517:prevention & control*
chemical_list: D019496:Cancer Vaccines; D050725:Papillomavirus E7 Proteins; D053918:Papillomavirus Vaccines; C059731:oncogene protein E7, Human papillomavirus type 16
keywords: CD8-positive T-lymphocytes; drug administration routes; immunotherapy; urinary bladder; urinary bladder neoplasms