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

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.
Proceedings of the National Academy of Sciences of the United States of America 2013 v.110 no.27 pp. 11103-11108
T-lymphocytes, animals, antibodies, antigen-presenting cells, antigens, cytotoxicity, immune response, macrophages, neoplasm cells, neoplasms, ovalbumin, phagocytosis
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.