CD47 blockade triggers T cell-mediated destruction of immunogenic tumors

Xiaojuan Liu, Yang Pu, Kyle Cron, Liufu Deng, Justin Kline, William A. Frazier, Hairong Xu, Hua Peng, Yang Xin Fu, Meng Michelle Xu

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)1209-1215
Number of pages7
JournalNature Medicine
Volume21
Issue number10
DOIs
StatePublished - Oct 1 2015

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T-cells
Tumors
T-Lymphocytes
Macrophages
Therapeutic Uses
Neoplasms
Cells
Cross-Priming
Cytophagocytosis
Blocking Antibodies
Chemotherapy
DNA
Heterografts
Dendritic Cells
Anti-Idiotypic Antibodies
Drug Therapy
Antibodies
Sensors
Therapeutics

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Liu, X., Pu, Y., Cron, K., Deng, L., Kline, J., Frazier, W. A., ... Xu, M. M. (2015). CD47 blockade triggers T cell-mediated destruction of immunogenic tumors. Nature Medicine, 21(10), 1209-1215. https://doi.org/10.1038/nm.3931

CD47 blockade triggers T cell-mediated destruction of immunogenic tumors. / Liu, Xiaojuan; Pu, Yang; Cron, Kyle; Deng, Liufu; Kline, Justin; Frazier, William A.; Xu, Hairong; Peng, Hua; Fu, Yang Xin; Xu, Meng Michelle.

In: Nature Medicine, Vol. 21, No. 10, 01.10.2015, p. 1209-1215.

Research output: Contribution to journalArticle

Liu, X, Pu, Y, Cron, K, Deng, L, Kline, J, Frazier, WA, Xu, H, Peng, H, Fu, YX & Xu, MM 2015, 'CD47 blockade triggers T cell-mediated destruction of immunogenic tumors', Nature Medicine, vol. 21, no. 10, pp. 1209-1215. https://doi.org/10.1038/nm.3931
Liu X, Pu Y, Cron K, Deng L, Kline J, Frazier WA et al. CD47 blockade triggers T cell-mediated destruction of immunogenic tumors. Nature Medicine. 2015 Oct 1;21(10):1209-1215. https://doi.org/10.1038/nm.3931
Liu, Xiaojuan ; Pu, Yang ; Cron, Kyle ; Deng, Liufu ; Kline, Justin ; Frazier, William A. ; Xu, Hairong ; Peng, Hua ; Fu, Yang Xin ; Xu, Meng Michelle. / CD47 blockade triggers T cell-mediated destruction of immunogenic tumors. In: Nature Medicine. 2015 ; Vol. 21, No. 10. pp. 1209-1215.
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