| Added by | tchardes |
|---|---|
| Group name | EquipeELC |
| Item Type | Journal Article |
| Title | Anti-cathepsin D immunotherapy triggers both innate and adaptive anti-tumour immunity in breast cancer |
| Creator | David et al. |
| Author | Timothée David |
| Author | Aude Mallavialle |
| Author | Julien Faget |
| Author | Lindsay B. Alcaraz |
| Author | Marion Lapierre |
| Author | Pénélope Desroys du Roure |
| Author | Valérie Laurent-Matha |
| Author | Hanane Mansouri |
| Author | Marta Jarlier |
| Author | Pierre Martineau |
| Author | Pascal Roger |
| Author | Séverine Guiu |
| Author | Thierry Chardès |
| Author | Emmanuelle Liaudet-Coopman |
| Abstract | 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. |
| Publication | British Journal of Pharmacology |
| Date | 2023-11-29 |
| Journal Abbr | Br J Pharmacol |
| Language | eng |
| DOI | 10.1111/bph.16291 |
| ISSN | 1476-5381 |
| Library Catalog | PubMed |
| Extra | PMID: 38030588 |
| Tags | anr, anti-tumour immunity, antibody-based therapy, biocampus, breast cancer, CLASSIFIED_ELC, first-last-corresponding, labex mabimprove, ligue, original, phd, post-doc, ram, rhem, TNBC, top, top ELC |
| Date Added | 2023/12/15 - 13:56:01 |
| Date Modified | 2025/01/13 - 10:37:28 |
| Notes and Attachments | PubMed entry (Attachment) |
Institut de Recherche en Cancérologie de
