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Nat Med. 2015 Oct;21(10):1209-15. doi: 10.1038/nm.3931. Epub 2015 Aug 31.

CD47 blockade triggers T cell-mediated destruction of immunogenic tumors.

Author information

1
Institute of Biophysics and the University of Chicago Joint Group for Immunotherapy, Chinese Academy of Science Key Laboratory for Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
2
University of Chinese Academy of Sciences, Beijing, China.
3
Department of Pathology and Committee on Immunology, University of Chicago, Chicago, Illinois, USA.
4
Department of Medicine and Committee on Immunology, University of Chicago, Chicago, Illinois, USA.
5
Department of Biochemistry and Molecular Biophysics, Washington University, St. Louis, Missouri, USA.

Abstract

Macrophage phagocytosis of tumor cells mediated by CD47-specific blocking antibodies has been proposed to be the major effector mechanism in xenograft models. Here, using syngeneic immunocompetent mouse tumor models, we reveal that the therapeutic effects of CD47 blockade depend on dendritic cell but not macrophage cross-priming of T cell responses. The therapeutic effects of anti-CD47 antibody therapy were abrogated in T cell-deficient mice. In addition, the antitumor effects of CD47 blockade required expression of the cytosolic DNA sensor STING, but neither MyD88 nor TRIF, in CD11c+ cells, suggesting that cytosolic sensing of DNA from tumor cells is enhanced by anti-CD47 treatment, further bridging the innate and adaptive responses. Notably, the timing of administration of standard chemotherapy markedly impacted the induction of antitumor T cell responses by CD47 blockade. Together, our findings indicate that CD47 blockade drives T cell-mediated elimination of immunogenic tumors.

PMID:
26322579
PMCID:
PMC4598283
DOI:
10.1038/nm.3931
[Indexed for MEDLINE]
Free PMC Article

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