title: A new strategy using autologous dendritic cells and lymphokine-activated killer cells for cancer immunotherapy: efficient maturation of DCs by co-culture with LAK cells in vitro.
abstract: Among a variety of antigen presenting cells (APCs), accumulating results support that the mature dendritic cell (DC) has the potential to induce efficient cytotoxic T lymphocyte (CTL) responses in the context of peptide-based immunotherapy. DCs have been known to assume the mature form by signaling through the CD40-CD40 ligand (CD40L) interaction, which may be provided by activated CD4+ T cells expressing abundant CD40L molecules on their surfaces. Here, we report that DCs generated from peripheral blood monocytes obtained from patients with advanced cancer exhibit a mature phenotype after co-culturing with autologous lymphokine-activated killer (LAK) cells generated by the stimulation of peripheral blood mononuclear cells with anti-CD3 monoclonal antibody (mAb) and interleukin (IL)-2. Part of this process appeared to be dependent on the expression of CD40L on the surface of LAK cells, although it was also suggested that some other humoral factors produced by LAK cells may be involved in this effect as well. DCs derived from the donors, of which LAK cells demonstrated a higher Th1/Th2 ratio upon activation determined by the intracellular detection of interferon-gamma and IL-4, showed more efficient maturation upon co-culture with LAK cells than DCs from donors with a low Th1/Th2 ratio. Importantly, these matured DCs induced a two-times stronger antigen-presenting capacity measured by an allo-reactive mixed lymphocytes reaction assay as compared to immature DCs. These results imply the use of the combination of DCs and LAK cells for immunotherapy against cancer.
authors.affiliation: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kyoto 602-8566, Japan.
authors.forename: Yutaro
authors.initials: Y
authors.lastname: Yano
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ueda
authors.forename: Tsuyohi
authors.initials: T
authors.lastname: Itoh
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Fuji
authors.forename: Kaori
authors.initials: K
authors.lastname: Okugawa
authors.forename: Kei
authors.initials: K
authors.lastname: Naito
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Imura
authors.forename: Junji
authors.initials: J
authors.lastname: Kohara
authors.forename: Takashi
authors.initials: T
authors.lastname: Hayashi
authors.forename: Kazuki
authors.initials: K
authors.lastname: Nakane
authors.forename: Yuko
authors.initials: Y
authors.lastname: Matsuura
authors.forename: Keiichi
authors.initials: K
authors.lastname: Kawai
authors.forename: Hisakazu
authors.initials: H
authors.lastname: Yamagishi
mesh_terms: D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D019013:CD40 Antigens / Q000096:biosynthesis; D017690:Cell Transplantation; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology*; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D015979:Killer Cells, Lymphokine-Activated / Q000166:cytology*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*
chemical_list: D019013:CD40 Antigens