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Anti-CD47 antibody–mediated phagocytosis of cancer by macrophages primes an effective antitumor T-cell response
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Anti-CD47 antibody–mediated phagocytosis of cancer by macrophages primes an effective antitumor T-cell response
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Journal Article
Anti-CD47 antibody–mediated phagocytosis of cancer by macrophages primes an effective antitumor T-cell response
2013
Overview
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.
Publisher
National Academy of Sciences,National Acad Sciences
Subject
/ Antibodies, Blocking - therapeutic use
/ Antibodies, Monoclonal - therapeutic use
/ Antigens
/ Cancer
/ CD8-Positive T-Lymphocytes - immunology
/ Colonic Neoplasms - immunology
/ Colonic Neoplasms - pathology
/ Cytotoxicity, Immunologic - genetics
/ Down-Regulation - immunology
/ Humans
/ Mice
/ Tumors
