Hiroki Goto1, Yuki Kojima2, Kouki Matsuda1, Ryusho Kariya1, Manabu Taura1, Kazuhiko Kuwahara3, Hirokazu Nagai2, Harutaka Katano4, Seiji Okada5. 1. Division of Hematopoiesis, Center for AIDS Research, Kumamoto University, Kumamoto, Japan. 2. Department of Hematology, National Hospital Organization Nagoya Medical Center, Nagaoya, Japan. 3. Department of Immunology, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan. 4. Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan. 5. Division of Hematopoiesis, Center for AIDS Research, Kumamoto University, Kumamoto, Japan. Electronic address: okadas@kumamoto-u.ac.jp.
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. CONCLUSION: 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.
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. CONCLUSION: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.
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