Anticancer effects of anti-CD47 immunotherapy in vivo

Kristina Iribarren, Aitziber Buque, Laura Mondragon, Wei Xie, Sarah Lévesque, Jonathan Pol, Laurence Zitvogel, Oliver Kepp, Guido Kroemer

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

The treatment of breast cancer largely depends on the utilization of immunogenic chemotherapeutics, which, as a common leitmotif, stimulate the exposure of calreticulin (CALR) on the surface of cancer cells, thereby facilitating their recognition by dendritic cells for the uptake of tumor-associated antigens and subsequent antigen cross-presentation to cytotoxic T cells. Breast cancer cells also express the calreticulin antagonist CD47, which inhibits tumor cell phagocytosis and consequently subverts anticancer immune responses. Here, we treated carcinogen-induced or transplantable mouse models of cancer by a CD47 blocking antibody that was at least as efficient as chemotherapy and that could be favorably combined with the anthracycline mitoxantrone in the context of carcinogen-induced orthotopic breast cancers. Monotherapy by CD47 blockade led to a reduction in tumor growth and an increase in overall survival. Of note, this treatment lead to a moderate depletion of M2 macrophages as well as close-to-complete elimination of regulatory T cells from the tumor bed, suggesting a strong favorable impact of CD47 blockade on the tumor microenvironment.

Original languageEnglish
Article number1550619
JournalOncoimmunology
Volume8
Issue number3
DOIs
StatePublished - Mar 4 2019
Externally publishedYes

Keywords

  • Anti-CD47
  • calreticulin
  • cancer
  • immune
  • therapeutic antibody

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