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

Autor: Magagna I; Equipe labellisée Ligue Nationale Contre le Cancer, Stress and Cancer Laboratory, Institut Curie, PSL Research University, 26, rue d'Ulm, 75005 Paris, France.; Inserm, U830, 75005 Paris, France.; Innate Pharma, 117 Avenue de Luminy BP 30191, 13276 Marseille, France., Gourdin N; Innate Pharma, 117 Avenue de Luminy BP 30191, 13276 Marseille, France., Kieffer Y; Equipe labellisée Ligue Nationale Contre le Cancer, Stress and Cancer Laboratory, Institut Curie, PSL Research University, 26, rue d'Ulm, 75005 Paris, France.; Inserm, U830, 75005 Paris, France., Licaj M; Equipe labellisée Ligue Nationale Contre le Cancer, Stress and Cancer Laboratory, Institut Curie, PSL Research University, 26, rue d'Ulm, 75005 Paris, France.; Inserm, U830, 75005 Paris, France., Mhaidly R; Equipe labellisée Ligue Nationale Contre le Cancer, Stress and Cancer Laboratory, Institut Curie, PSL Research University, 26, rue d'Ulm, 75005 Paris, France.; Inserm, U830, 75005 Paris, France., Andre P; Innate Pharma, 117 Avenue de Luminy BP 30191, 13276 Marseille, France., Morel A; Innate Pharma, 117 Avenue de Luminy BP 30191, 13276 Marseille, France., Vincent-Salomon A; Hospital Group, Department of Diagnostic and Theranostic Medicine, Institut Curie, 75005 Paris, France., Paturel C; Innate Pharma, 117 Avenue de Luminy BP 30191, 13276 Marseille, France., Mechta-Grigoriou F; Equipe labellisée Ligue Nationale Contre le Cancer, Stress and Cancer Laboratory, Institut Curie, PSL Research University, 26, rue d'Ulm, 75005 Paris, France.; Inserm, U830, 75005 Paris, France.
Jazyk: angličtina
Zdroj: Cancers [Cancers (Basel)] 2021 Nov 23; Vol. 13 (23). Date of Electronic Publication: 2021 Nov 23.
DOI: 10.3390/cancers13235878
Abstrakt: 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.
Databáze: MEDLINE
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