title: Anti-CD47 antibody-mediated phagocytosis of cancer by macrophages primes an effective antitumor T-cell response.
abstract: Mobilization of the T-cell response against cancer has the potential to achieve long-lasting cures. However, it is not known how to harness antigen-presenting cells optimally to achieve an effective antitumor T-cell response. In this study, we show that anti-CD47 antibody-mediated phagocytosis of cancer by macrophages can initiate an antitumor T-cell immune response. Using the ovalbumin model antigen system, anti-CD47 antibody-mediated phagocytosis of cancer cells by macrophages resulted in increased priming of OT-I T cells [cluster of differentiation 8-positive (CD8(+))] but decreased priming of OT-II T cells (CD4(+)). The CD4(+) T-cell response was characterized by a reduction in forkhead box P3-positive (Foxp3(+)) regulatory T cells. Macrophages following anti-CD47-mediated phagocytosis primed CD8(+) T cells to exhibit cytotoxic function in vivo. This response protected animals from tumor challenge. We conclude that anti-CD47 antibody treatment not only enables macrophage phagocytosis of cancer but also can initiate an antitumor cytotoxic T-cell immune response.
authors.affiliation: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University Medical Center, Stanford, CA 94305, USA. dianet@gmail.com
authors.forename: Diane
authors.initials: D
authors.lastname: Tseng
authors.forename: Jens-Peter
authors.initials: JP
authors.lastname: Volkmer
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Willingham
authors.forename: Humberto
authors.initials: H
authors.lastname: Contreras-Trujillo
authors.forename: John W
authors.initials: JW
authors.lastname: Fathman
authors.forename: Nathaniel B
authors.initials: NB
authors.lastname: Fernhoff
authors.forename: Jun
authors.initials: J
authors.lastname: Seita
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Inlay
authors.forename: Kipp
authors.initials: K
authors.lastname: Weiskopf
authors.forename: Masanori
authors.initials: M
authors.lastname: Miyanishi
authors.forename: Irving L
authors.initials: IL
authors.lastname: Weissman
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D051928:CD47 Antigen / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D006801:Humans; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010587:Phagocytosis / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology; D023041:Xenograft Model Antitumor Assays
chemical_list: D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D051928:CD47 Antigen; C497894:CD47 protein, human