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

作者：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.

来源：Proceedings of the National Academy of Sciences, 2013, 110(27): 11103-11108.

DOI：10.1073/pnas.1305569110

• DENDRITIC CELLS
• PROTEIN-ALPHA
• PROMOTE PHAGOCYTOSIS
• DOWN-REGULATION
• CD47
• CALRETICULIN
• CONTRIBUTES
• INHIBITION
• ANTIGENS
• TARGET

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.

• 出版日期2013-7-2