title: Efficacy of anti-CD47 antibody-mediated phagocytosis with macrophages against primary effusion lymphoma.
abstract: BACKGROUND
  Recently, the critical role of CD47 on the surface of resistant cancer cells has been proposed in their evasion of immunosurveillance. Primary effusion lymphoma (PEL) is a subtype of aggressive non-Hodgkin lymphoma that shows serous lymphomatous effusion in body cavities, especially in advanced acquired immunodeficiency syndrome (AIDS). PEL is resistant to conventional chemotherapy and has a poor prognosis. In this study, we evaluated the effect of anti-CD47 antibody (Ab) on PEL in vitro and in vivo.
  
  
  METHODS
  Surface CD47 of PEL cell lines was examined by flow cytometry. Efficacy of knocking down CD47 or anti-CD47 Ab-mediated phagocytosis against PEL was evaluated using mouse peritoneal macrophages and human macrophages in vitro. Primary PEL cells were injected intraperitoneally into NOD/Rag-2/Jak3 double-deficient (NRJ) mice to establish a direct xenograft mouse model.
  
  
  RESULTS
  Surface CD47 of PEL cell lines was highly expressed. Knocking down CD47 and anti-CD47 Ab promoted phagocytic activities of macrophages in a CD47 expression-dependent manner in vitro. Treatment with anti-CD47 Ab inhibited ascite formation and organ invasion completely in vivo compared with control IgG-treated mice.
  
  
  CONCLUSIONS
  CD47 plays the pivotal role in the immune evasion of PEL cells in body cavities. Therapeutic antibody targeting of CD47 could be an effective therapy for PEL.
authors.affiliation: Division of Hematopoiesis, Center for AIDS Research, Kumamoto University, Kumamoto, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Goto
authors.affiliation: Department of Hematology, National Hospital Organization Nagoya Medical Center, Nagaoya, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kojima
authors.affiliation: Division of Hematopoiesis, Center for AIDS Research, Kumamoto University, Kumamoto, Japan.
authors.forename: Kouki
authors.initials: K
authors.lastname: Matsuda
authors.affiliation: Division of Hematopoiesis, Center for AIDS Research, Kumamoto University, Kumamoto, Japan.
authors.forename: Ryusho
authors.initials: R
authors.lastname: Kariya
authors.affiliation: Division of Hematopoiesis, Center for AIDS Research, Kumamoto University, Kumamoto, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Taura
authors.affiliation: Department of Immunology, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Kuwahara
authors.affiliation: Department of Hematology, National Hospital Organization Nagoya Medical Center, Nagaoya, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Nagai
authors.affiliation: Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Harutaka
authors.initials: H
authors.lastname: Katano
authors.affiliation: Division of Hematopoiesis, Center for AIDS Research, Kumamoto University, Kumamoto, Japan. Electronic address: okadas@kumamoto-u.ac.jp.
authors.forename: Seiji
authors.initials: S
authors.lastname: Okada
mesh_terms: D000328:Adult; D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D051928:CD47 Antigen / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D018920:Coculture Techniques; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics; D055785:Gene Knockdown Techniques; D006801:Humans; D053616:Janus Kinase 3 / Q000172:deficiency / Q000235:genetics; D054685:Lymphoma, Primary Effusion / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D009361:Neoplasm Invasiveness; D010587:Phagocytosis / Q000187:drug effects*; D034622:RNA Interference; D014162:Transfection; D019139:Tumor Escape / Q000187:drug effects*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000906:Antibodies; D000970:Antineoplastic Agents; D051928:CD47 Antigen; C497894:CD47 protein, human; C497895:Cd47 protein, mouse; D004268:DNA-Binding Proteins; C499308:Rag2 protein, mouse; C507935:Jak3 protein, mouse; D053616:Janus Kinase 3
keywords: AIDS; CD47; Macrophage; Mouse model; Primary effusion lymphoma