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. 2025 Jan 1;156(1):229-242.
doi: 10.1002/ijc.35107. Epub 2024 Jul 30.

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

Cédric Lerévérend  1 , Nour Kotaich  1 , Lucille Cartier  2 , Manon De Boni  2 , Sarah Lahire  1 , Caroline Fichel  1 , Charlotte Thiebault  1 , Eva Brabencova  3 , Célia Maquin  3 , Elodie Barbosa  3 , Laurent Corsois  2 , Judicael Hotton  4 , Sofiane Guendouzen  5 , Philippe Guilbert  5 , Aude-Marie Lepagnol-Bestel  1 , Laurence Cahen-Doidy  6 , Jacqueline Lehmann-Che  6   7 , Jérôme Devy  8   9 , Armand Bensussan  6 , Sébastien Le Jan  1 , Arnaud Pommier  1 , Yacine Merrouche  1   2 , Richard Le Naour  1 , Stéphane Vignot  1   2 , Stephane Potteaux  1   2   10
Affiliations

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

Cédric Lerévérend et al. Int J Cancer. .

Abstract

Optimizations 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.

Keywords: galectin‐9; molecular targeted therapy; radiotherapy; triple‐negative breast cancer.

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