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Magagna I, Gourdin N, Kieffer Y, et al. CD73-Mediated Immunosuppression Is Linked to a Specific Fibroblast Population That Paves the Way for New Therapy in Breast Cancer. Cancers (Basel). 2021;13(23)doi: 10.3390/cancers13235878.
Magagna, I., Gourdin, N., Kieffer, Y., Licaj, M., Mhaidly, R., Andre, P., Morel, A., Vincent-Salomon, A., Paturel, C., & Mechta-Grigoriou, F. (2021). CD73-Mediated Immunosuppression Is Linked to a Specific Fibroblast Population That Paves the Way for New Therapy in Breast Cancer. Cancers, 13(23), . https://doi.org/10.3390/cancers13235878
Magagna, Ilaria, et al. "CD73-Mediated Immunosuppression Is Linked to a Specific Fibroblast Population That Paves the Way for New Therapy in Breast Cancer." Cancers vol. 13,23 (2021). doi: https://doi.org/10.3390/cancers13235878
Magagna I, Gourdin N, Kieffer Y, Licaj M, Mhaidly R, Andre P, Morel A, Vincent-Salomon A, Paturel C, Mechta-Grigoriou F. CD73-Mediated Immunosuppression Is Linked to a Specific Fibroblast Population That Paves the Way for New Therapy in Breast Cancer. Cancers (Basel). 2021 Nov 23;13(23). doi: 10.3390/cancers13235878. PMID: 34884993.
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Cancers (Basel). 2021 Nov 23;13(23). doi: 10.3390/cancers13235878.

CD73-Mediated Immunosuppression Is Linked to a Specific Fibroblast Population That Paves the Way for New Therapy in Breast Cancer.

Cancers

Ilaria Magagna, Nicolas Gourdin, Yann Kieffer, Monika Licaj, Rana Mhaidly, Pascale Andre, Ariane Morel, Anne Vincent-Salomon, Carine Paturel, Fatima Mechta-Grigoriou

Affiliations

  1. Equipe labellisée Ligue Nationale Contre le Cancer, Stress and Cancer Laboratory, Institut Curie, PSL Research University, 26, rue d'Ulm, 75005 Paris, France.
  2. Inserm, U830, 75005 Paris, France.
  3. Innate Pharma, 117 Avenue de Luminy BP 30191, 13276 Marseille, France.
  4. Hospital Group, Department of Diagnostic and Theranostic Medicine, Institut Curie, 75005 Paris, France.

PMID: 34884993 DOI: 10.3390/cancers13235878

Abstract

BACKGROUND: Cancer-associated fibroblasts (CAF) are heterogeneous with multiple functions in breast cancer. Recently, we identified a specific CAF subpopulation (referred to as CAF-S1), which promotes immunosuppression and immunotherapy resistance.

METHODS AND RESULTS: Here, by studying a large collection of human samples, we highlight the key function of CD73/NT5E in CAF-S1-mediated immunosuppression in breast cancer. We first reveal that CD73 protein level specifically accumulates in CAF-S1 in breast cancer patients. Interestingly, infiltration of regulatory T lymphocytes (Tregs) is significantly correlated with CD73 expression in stroma but not in epithelium, indicating that CD73 contributes to immunosuppression when expressed in CAF-S1 and not in tumor cells. By performing functional assays based on relevant systems using primary CAF-S1 isolated from patients, we demonstrate that CAF-S1 increase the content in both PD-1+ and CTLA-4+ Tregs. Importantly, the use of a blocking anti-CD73 antibody on CAF-S1 reduces CAF-S1-mediated immunosuppression by preventing expression of these immune checkpoints on Tregs.

CONCLUSIONS: Our data support the potential clinical benefit of using both anti-CD73 and immune-checkpoint inhibitors in breast cancer patients for inhibiting CAF-S1-mediated immunosuppression and enhancing anti-tumor immune response.

Keywords: CAF subsets; Tregs; anti-CD73 antibody; breast cancer; immunosuppression

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