Academic Journal
Anti-cathepsin D immunotherapy triggers both innate and adaptive anti-tumour immunity in breast cancer ; Anti-cathepsin D immunotherapy triggers both innate and adaptive anti-tumour immunity in breast cancer: Antibody-based immunomodulatory therapy of breast cancer
| العنوان: | Anti-cathepsin D immunotherapy triggers both innate and adaptive anti-tumour immunity in breast cancer ; Anti-cathepsin D immunotherapy triggers both innate and adaptive anti-tumour immunity in breast cancer: Antibody-based immunomodulatory therapy of breast cancer |
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| المؤلفون: | David, Timothée, Mallavialle, Aude, Faget, Julien, Alcaraz, Lindsay, B, Lapierre, Marion, Du Roure, Pénélope Desroys, Laurent-Matha, Valérie, Mansouri, Hanane, Jarlier, Marta, Martineau, Pierre, Roger, Pascal, Guiu, Séverine, Chardès, Thierry, Liaudet-Coopman, Emmanuelle |
| المساهمون: | Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), UNICANCER - Institut régional du Cancer Montpellier Val d'Aurelle (ICM), CRLCC Val d'Aurelle - Paul Lamarque, Hôpital Universitaire Carémeau Nîmes (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Institut régional de Cancérologie de Montpellier (ICM), Centre National de la Recherche Scientifique (CNRS), This work was supported by a public grant overseen by the French National Research Agency (ANR) as part of the “Investissements d’Avenir” program (reference: LabEx MabImprove ANR-10-LABX-53-01), University of Montpellier, Inserm Transfert, Région Occitanie, ‘Ligue Nationale contre le Cancer’, the associations ‘Ligue Régionale du Gard’, ‘Ligue Régionale de l’Herault’, and ‘Ligue Régionale de la Charente Maritime. We acknowledge the “Réseau d’Histologie Expérimentale de Montpellier” - RHEM facility supported by SIRIC Montpellier Cancer Grant INCa_Inserm_DGOS_12553, the European regional development foundation and the Occitanie region (FEDER-FSE 2014-2020 Languedoc Roussillon), REACT-EU (Recovery Assistance for Cohesion and the Territories of Europe), IBiSA and Ligue contre le cancer for processing/analyzing our animal tissues with expertise. |
| المصدر: | ISSN: 0007-1188. |
| بيانات النشر: | HAL CCSD Wiley |
| سنة النشر: | 2023 |
| المجموعة: | Université de Montpellier: HAL |
| مصطلحات موضوعية: | tumour microenvironment, anti-tumour immunity, TNBC, breast cancer, antibody-based therapy, immunomodulation, protease, [SDV]Life Sciences [q-bio] |
| الوصف: | International audience ; Background and purpose: Triple-negative breast cancer (TNBC) has poorer outcomes than other breast cancer (BC) subtypes, including HER2+ BC. Cathepsin D (CathD) is a poor prognosis marker overproduced by BC cells and hypersecreted in the tumour microenvironment with tumour-promoting activity. Here, we characterized the immunomodulatory activity of the anti-CathD antibody F1 and of its improved Fab-aglycosylated version (F1M1) in immunocompetent mouse models of TNBC (C57BL/6 mice harbouring E0771 cell grafts) and HER2-amplified BC (BALB/c mice harbouring TUBO cell grafts).Experimental approach: CathD expression was evaluated by western blotting and immunofluorescence, and antibody binding to CathD by ELISA. The antibody anti-tumour efficacy was investigated in mouse models. Immune cell recruitment and activation were assessed by immunohistochemistry, immunophenotyping, and RT-qPCR.Key results: Both F1 and F1M1 antibodies remodelled the tumour immune landscape. Both antibodies promoted the innate antitumour immunity by preventing the recruitment of immunosuppressive M2-polarized tumour-associated macrophages (TAMs) and by activating natural killer cells in the tumour microenvironment of both models. This translated into a reduction of T-cell exhaustion markers in the tumour microenvironment that could be locally supported by enhanced activation of anti-tumour antigen-presenting cell (M1-polarized TAMs and cDC1 cells) functions. Both antibodies inhibited tumour growth in the highly-immunogenic E0771 model, but only marginally in the immune-excluded TUBO model, indicating that anti-CathD immunotherapy is more relevant for BC with a high immune cell infiltrate, as often observed in TNBC.Conclusion and implication: Anti-CathD antibody-based therapy triggers the anti-tumour innate and adaptive immunity in preclinical models of BC, and is a promising immunotherapy for immunogenic TNBC. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1111/bph.16291 |
| الاتاحة: | https://hal.science/hal-04295033 https://hal.science/hal-04295033v1/document https://hal.science/hal-04295033v1/file/David%20et%20al.%20Biochem%20J%20Pharmacol%202023%20-%20Version%20HAL.pdf https://doi.org/10.1111/bph.16291 |
| Rights: | info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.2F45CF11 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1111/bph.16291 |
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