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

D Tseng, JP Volkmer, SB Willingham… - Proceedings of the …, 2013 - National Acad Sciences
D Tseng, JP Volkmer, SB Willingham, H Contreras-Trujillo, JW Fathman, NB Fernhoff…
Proceedings of the National Academy of Sciences, 2013National Acad Sciences
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 …
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.
National Acad Sciences