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

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

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.

MeSH terms

  • Animals
  • Biomarkers, Tumor / metabolism
  • Cell Line, Tumor
  • Female
  • Galectins* / metabolism
  • Humans
  • Mice
  • Mice, Inbred BALB C*
  • Middle Aged
  • Molecular Targeted Therapy
  • Neoadjuvant Therapy / methods
  • Triple Negative Breast Neoplasms* / metabolism
  • Triple Negative Breast Neoplasms* / pathology
  • Triple Negative Breast Neoplasms* / radiotherapy
  • Xenograft Model Antitumor Assays

Substances

  • Galectins
  • LGALS9 protein, human
  • Biomarkers, Tumor