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

IF 5.7 2区 医学 Q1 ONCOLOGY
Cédric Lerévérend, Nour Kotaich, Lucille Cartier, Manon De Boni, Sarah Lahire, Caroline Fichel, Charlotte Thiebault, Eva Brabencova, Célia Maquin, Elodie Barbosa, Laurent Corsois, Judicael Hotton, Sofiane Guendouzen, Philippe Guilbert, Aude-Marie Lepagnol-Bestel, Laurence Cahen-Doidy, Jacqueline Lehmann-Che, Jérôme Devy, Armand Bensussan, Sébastien Le Jan, Arnaud Pommier, Yacine Merrouche, Richard Le Naour, Stéphane Vignot, Stephane Potteaux
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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.

放疗后三阴性乳腺癌细胞中 galectin-9 的表达增强:靶向治疗的意义
治疗三阴性乳腺癌(TNBC)的免疫疗法有望得到优化。我们研究了照射后galectin-9(Gal-9)的表达,并评估了放疗与否对其靶向性的不同影响。接受新辅助放疗的 TNBC 患者切除的肿瘤显示,与基线水平相比,只有非应答患者的 Gal-9 水平更高。研究还发现,TNBC肿瘤活检组织和细胞系在接受照射后,Gal-9的表达也有所增加。我们研究了小鼠放疗后靶向 Gal-9 的治疗优势。将经过辐照的 4T1 细胞或对照组未经过辐照的 4T1 细胞注射到 BALB/c 小鼠体内。抗Gal-9抗体治疗只对注射了辐照过的4T1细胞的小鼠有抑制肿瘤进展的作用。这项概念验证研究表明,Gal-9可被视为TNBC放疗后的动态生物标志物,并表明Gal-9诱导的过表达可能是为TNBC患者开发新治疗策略的一个机会。
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来源期刊
CiteScore
13.40
自引率
3.10%
发文量
460
审稿时长
2 months
期刊介绍: The International Journal of Cancer (IJC) is the official journal of the Union for International Cancer Control—UICC; it appears twice a month. IJC invites submission of manuscripts under a broad scope of topics relevant to experimental and clinical cancer research and publishes original Research Articles and Short Reports under the following categories: -Cancer Epidemiology- Cancer Genetics and Epigenetics- Infectious Causes of Cancer- Innovative Tools and Methods- Molecular Cancer Biology- Tumor Immunology and Microenvironment- Tumor Markers and Signatures- Cancer Therapy and Prevention
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