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Anti-CD47 antibody–mediated phagocytosis of cancer by macrophages primes an effective antitumor T-cell response

Author:
Tseng, Diane, Volkmer, Jens-Peter, Willingham, Stephen B., Contreras-Trujillo, Humberto, Fathman, John W., Fernhoff, Nathaniel B., Seita, Jun, Inlay, Matthew A., Weiskopf, Kipp, Miyanishi, Masanori, Weissman, Irving L.
Source:
Proceedings of the National Academy of Sciences of the United States of America 2013 v.110 no.27 pp. 11103-11108
ISSN:
0027-8424
Subject:
T-lymphocytes, animals, antibodies, antigen-presenting cells, antigens, cytotoxicity, immune response, macrophages, neoplasm cells, neoplasms, ovalbumin, phagocytosis
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.
Agid:
1737236