Institute for Stem Cell Biology and Regenerative Medicine, Stanford University Medical Center, Stanford, CA 94305, USA.
Proc Natl Acad Sci U S A. 2013 Jul 2;110(27):11103-8. doi: 10.1073/pnas.1305569110. Epub 2013 May 20.
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.
针对癌症的 T 细胞反应的动员具有实现长期治愈的潜力。然而，目前尚不清楚如何最佳地利用抗原呈递细胞来实现有效的抗肿瘤 T 细胞反应。在这项研究中，我们表明，巨噬细胞通过抗 CD47 抗体介导的吞噬作用来吞噬癌症，可以引发抗肿瘤 T 细胞免疫反应。使用卵清蛋白模型抗原系统，巨噬细胞通过抗 CD47 抗体介导的吞噬作用吞噬癌细胞，导致 OT-I T 细胞（CD8+）的初始激活增加，但 OT-II T 细胞（CD4+）的初始激活减少。CD4+T 细胞反应的特征是叉头框 P3 阳性（Foxp3+）调节性 T 细胞减少。抗 CD47 介导的吞噬作用后的巨噬细胞将 CD8+T 细胞初始激活为体内具有细胞毒性功能。这种反应使动物免受肿瘤挑战。我们得出结论，抗 CD47 抗体治疗不仅能够使巨噬细胞吞噬癌症，还可以引发抗肿瘤细胞毒性 T 细胞免疫反应。
