title: Phagocytosis of bafilomycin A1-treated apoptotic neuroblastoma cells by bone marrow-derived dendritic cells initiates a CD8α+ lymphocyte response to neuroblastoma.
abstract: This study aimed to determine whether bafilomycin A1 (Baf-A1), a vacuolar H-ATPase inhibitor, could promote an immune response after the induction of apoptosis in mouse neuroblastoma cells. Mouse neuro-2a cells were cultured in a medium containing Baf-A1, and apoptosis was evaluated by flow cytometry. To examine the influence in the phagocytic cell, CD11b spleen cells or bone marrow-derived dendritic cells (BM-DCs) were cocultured with Baf-A1-treated neuro-2a. Interferon-γ (IFN-γ) production was used as an index of the immune response, and CDDP was used as the negative control. When CD8α cells were cocultured with CD11b cells and Baf-A1-treated neuro-2a cells in the presence of CpG-oligodeoxynucleotide (CpG-ODN) (a toll-like receptor 9 [TLR-9] agonist), CD8α lymphocyte proliferation and secretion of IFN-γ were observed. Phagocytosis of apoptotic cells by BM-DCs was maximal after simultaneous stimulation with CpG-ODN and lipopolysaccharide (LPS; a TLR-4 agonist). IFN-γ secretion was maximal when Baf-A1-treated neuro-2a cells and CD8α lymphocytes were cocultured with BM-DCs and stimulated with CpG-ODN. In contrast, IFN-γ production was not increased when the cells were cultured with LPS. When cells were stimulated with both CpG-ODN and LPS, promotion of IFN-γ production by CpG-ODN was suppressed. Induction of apoptosis by Baf-A1 could possibly enhance antitumor immunity in patients receiving chemotherapy for neuroblastoma. Stimulation of BM-DCs with a TLR-9 agonist could promote antitumor activity after Baf-A1 treatment.
authors: Departments of *Hepato-Billiary-Pancreatic and Pediatric Surgery †Medical Research, Saitama Medical Center, Saitama Medical University, Kawagoe, Saitama, Japan.
authors: Seiichiro
authors: S
authors: Inoue
authors: Yumiko
authors: Y
authors: Setoyama
authors: Akio
authors: A
authors: Odaka
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D017209:Apoptosis / Q000187:drug effects*; D001854:Bone Marrow Cells; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D049109:Cell Proliferation; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D018942:Macrolides / Q000494:pharmacology*; D051379:Mice; D008805:Mice, Inbred A; D009447:Neuroblastoma / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D010587:Phagocytosis / Q000502:physiology*; D014407:Tumor Cells, Cultured
chemical_list: C408982:CPG-oligonucleotide; D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D018942:Macrolides; D009838:Oligodeoxyribonucleotides; D007371:Interferon-gamma; C040929:bafilomycin A1