https://orcid.org/0000-0002-2930-8573
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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.
Abbreviations
| CALR | = | calreticulin |
| DC | = | dendritic cell |
| ICD | = | immunogenic cell death |
| ip | = | intraperitoneal |
Acknowledgments
GK is supported by the Ligue contre le Cancer (équipe labellisée); Agence National de la Recherche (ANR) – Projets blancs; Association pour la recherche sur le cancer (ARC); Cancéropôle Ile-de-France; Chancelerie des universités de Paris (Legs Poix); Fondation pour la Recherche Médicale (FRM); the European Research Council (ERC); Institut National du Cancer (INCa); Inserm (HTE); Institut Universitaire de France; the LabEx Immuno-Oncology; the RHU Torino Lumière; the SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE); the SIRIC Cancer Research and Personalized Medicine (CARPEM), as well as Vasculox Ltd. LZ was supported by Ligue contre le Cancer (équipe labellisée), RHU TORINO-LUMIERE, Swiss Bridge Foundation, ARC and LabEx Immuno-Oncology.
Conflicts of interest
This work was partially funded by Tioma Therapeutics.
Supplementary Material
Supplemental data for this article can be accessed here.