Enhanced expression of galectin‐9 in triple negative breast cancer cells following radiotherapy: Implications for targeted therapy

Author:

Lerévérend Cédric1,Kotaich Nour1,Cartier Lucille2,De Boni Manon2,Lahire Sarah1,Fichel Caroline1,Thiebault Charlotte1,Brabencova Eva3,Maquin Célia3,Barbosa Elodie3,Corsois Laurent2,Hotton Judicael4,Guendouzen Sofiane5,Guilbert Philippe5,Lepagnol‐Bestel Aude‐Marie1,Cahen‐Doidy Laurence6,Lehmann‐Che Jacqueline67,Devy Jérôme89,Bensussan Armand6,Le Jan Sébastien1,Pommier Arnaud1,Merrouche Yacine12,Le Naour Richard1,Vignot Stéphane12,Potteaux Stephane1210ORCID

Affiliation:

1. Université de Reims Champagne Ardenne, IRMAIC UR 7509 Reims France

2. Département de Recherche Institut Godinot Reims France

3. Centre de ressources biologiques, Institut Godinot Reims France

4. Département de chirurgie oncologique Institut Godinot Reims France

5. Département de radiothérapie Institut Godinot Reims France

6. Université Paris Cité, INSERM, U976 HIPI Paris France

7. Molecular Oncology Unit, Saint Louis Hospital, APHP Paris France

8. Matrice Extracellulaire et Dynamique Cellulaire, MEDyC, UMR 7369 CNRS Reims France

9. Université de Reims Champagne‐Ardenne, UFR Sciences Exactes et Naturelles, Reims Cedex France

10. Inserm, Délégation régionale Paris Île‐de‐France Centre Nord Paris France

Abstract

AbstractOptimizations are expected in the development of immunotherapy for the treatment of Triple‐negative breast cancer (TNBC). We studied the expression of galectin‐9 (Gal‐9) after irradiation and assessed the differential impacts of its targeting with or without radiotherapy. Tumor resections from TNBC patients who received neoadjuvant radiotherapy revealed higher levels of Gal‐9 in comparison to their baseline level, only in non‐responder patients. Gal‐9 expression was also found to be increased in TNBC tumor biopsies and cell lines after irradiation. We investigated the therapeutic advantage of targeting Gal‐9 after radiotherapy in mice. Irradiated 4T1 cells or control non‐irradiated 4T1 cells were injected into BALB/c mice. Anti‐Gal‐9 antibody treatment decreased tumor progression only in mice injected with irradiated 4T1 cells. This proof‐of‐concept study demonstrates that Gal‐9 could be considered as a dynamic biomarker after radiotherapy for TNBC and suggests that Gal‐9 induced‐overexpression could represent an opportunity to develop new therapeutic strategies for TNBC patients.

Publisher

Wiley

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