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

TLDR

Effective antitumor T‑cell responses could cure cancer, but optimal use of antigen‑presenting cells remains unclear. The study demonstrates that anti‑CD47 antibody–mediated macrophage phagocytosis can trigger an antitumor T‑cell response. Anti‑CD47 antibody–mediated phagocytosis enhanced CD8+ T‑cell priming, reduced CD4+ T‑cell and regulatory T‑cell responses, and produced cytotoxic CD8+ T cells that protected mice from tumor challenge, indicating that this therapy initiates an effective antitumor cytotoxic T‑cell response.

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.