title: Simultaneous activation of T helper function can augment the potency of dendritic cell-based cancer immunotherapy.
abstract: OBJECTIVE
  Simultaneous activation of T helper 1 (Th1) cell function has crucial roles in induction of potent cytotoxic T lymphocyte (CTL) responses in cancer immunotherapy. Here, we investigated whether dendritic cell (DC)-based vaccines loaded with both tumor-associated antigen (TAA)-derived MHC class I and pan-MHC class II peptides could elicit more potent CTL responses through simultaneous activation of Th1 function and reduction in CD4(+) regulatory T (Treg) cell proliferation.
  
  
  METHODS
  C57BL/6 mice bearing LLC1, a mouse Lewis lung cancer cell line, were subcutaneously administered DCs loaded with both LLC-derived MHC class I (MUT1&2) and LLC-unrelated pan-MHC class II (PADRE) peptides (DC-MUT1&2-PADRE). In assays using samples from advanced lung cancer patients, peripheral blood mononuclear cells were stimulated with autologous DCs loaded with both MUC1 MHC class I and PADRE peptides (DC-MUC1-PADRE) in vitro. Subsequently, TAA-specific CTL responses and the population of CD4(+) Treg cells were analyzed.
  
  
  RESULTS
  The population of spleen CD4(+) PADRE-specific cells producing interferon-gamma (IFNγ) was significantly increased by DC-MUT1&2-PADRE administration. Vaccinations with DC-MUT1&2-PADRE decreased the population of CD4(+) Treg cells in spleen and augmented CTL responses, effectively leading to suppression of tumor growth. In assays with human samples, CD4(+) Treg cells were induced less frequently, and MUC1-specific cytotoxicity was enhanced by stimulation with DC-MUC1-PADRE compared with that by stimulation with DC-MUC1 alone.
  
  
  CONCLUSIONS
  Simultaneous activation of Th1 function by DCs loaded with both TAA-derived MHC class I and PADRE peptides augments TAA-specific CTL responses while reducing Treg cell proliferation.
authors: Department of Surgery, Shiga University of Medical Science, Seta-Tsukinowa, Otsu, Shiga 520-2192, Japan. teramoto@belle.shiga-med.ac.jp
authors: Koji
authors: K
authors: Teramoto
authors: Yasuhiko
authors: Y
authors: Ohshio
authors: Takuya
authors: T
authors: Fujita
authors: Jun
authors: J
authors: Hanaoka
authors: Keiichi
authors: K
authors: Kontani
mesh_terms: D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000737:chemistry / Q000276:immunology; D006801:Humans; D007167:Immunotherapy; D007371:Interferon-gamma / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy; D010455:Peptides / Q000276:immunology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology
chemical_list: D019496:Cancer Vaccines; D000949:Histocompatibility Antigens Class II; D010455:Peptides; D007371:Interferon-gamma