دورية أكاديمية
Netrin-1 blockade inhibits tumor associated Myeloid-derived suppressor cells, cancer stemness and alleviates resistance to chemotherapy and immune checkpoint inhibitor.
العنوان: | Netrin-1 blockade inhibits tumor associated Myeloid-derived suppressor cells, cancer stemness and alleviates resistance to chemotherapy and immune checkpoint inhibitor. |
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المؤلفون: | Ducarouge B; Apoptosis, Cancer and Development Laboratory- Equipe labellisée 'La Ligue', Labex DEVweCAN, Institut Convergence PLAsCAN, Centre de Cancérologie de Lyon, INSERM U1052-CNRS UMR5286, Université de Lyon, Centre Léon Bérard, 69008, Lyon, France.; Netris Pharma, Centre Léon Bérard, 69008, Lyon, France., Redavid AR; Apoptosis, Cancer and Development Laboratory- Equipe labellisée 'La Ligue', Labex DEVweCAN, Institut Convergence PLAsCAN, Centre de Cancérologie de Lyon, INSERM U1052-CNRS UMR5286, Université de Lyon, Centre Léon Bérard, 69008, Lyon, France., Victoor C; Apoptosis, Cancer and Development Laboratory- Equipe labellisée 'La Ligue', Labex DEVweCAN, Institut Convergence PLAsCAN, Centre de Cancérologie de Lyon, INSERM U1052-CNRS UMR5286, Université de Lyon, Centre Léon Bérard, 69008, Lyon, France.; Netris Pharma, Centre Léon Bérard, 69008, Lyon, France., Chira R; Apoptosis, Cancer and Development Laboratory- Equipe labellisée 'La Ligue', Labex DEVweCAN, Institut Convergence PLAsCAN, Centre de Cancérologie de Lyon, INSERM U1052-CNRS UMR5286, Université de Lyon, Centre Léon Bérard, 69008, Lyon, France.; Netris Pharma, Centre Léon Bérard, 69008, Lyon, France., Fonseca A; Research Pathology Department, Centre Léon Bérard, Lyon, France., Hervieu M; Apoptosis, Cancer and Development Laboratory- Equipe labellisée 'La Ligue', Labex DEVweCAN, Institut Convergence PLAsCAN, Centre de Cancérologie de Lyon, INSERM U1052-CNRS UMR5286, Université de Lyon, Centre Léon Bérard, 69008, Lyon, France., Bergé R; Apoptosis, Cancer and Development Laboratory- Equipe labellisée 'La Ligue', Labex DEVweCAN, Institut Convergence PLAsCAN, Centre de Cancérologie de Lyon, INSERM U1052-CNRS UMR5286, Université de Lyon, Centre Léon Bérard, 69008, Lyon, France.; Netris Pharma, Centre Léon Bérard, 69008, Lyon, France., Lengrand J; Apoptosis, Cancer and Development Laboratory- Equipe labellisée 'La Ligue', Labex DEVweCAN, Institut Convergence PLAsCAN, Centre de Cancérologie de Lyon, INSERM U1052-CNRS UMR5286, Université de Lyon, Centre Léon Bérard, 69008, Lyon, France.; Netris Pharma, Centre Léon Bérard, 69008, Lyon, France., Vieugué P; Apoptosis, Cancer and Development Laboratory- Equipe labellisée 'La Ligue', Labex DEVweCAN, Institut Convergence PLAsCAN, Centre de Cancérologie de Lyon, INSERM U1052-CNRS UMR5286, Université de Lyon, Centre Léon Bérard, 69008, Lyon, France., Neves D; Netris Pharma, Centre Léon Bérard, 69008, Lyon, France., Goddard I; Apoptosis, Cancer and Development Laboratory- Equipe labellisée 'La Ligue', Labex DEVweCAN, Institut Convergence PLAsCAN, Centre de Cancérologie de Lyon, INSERM U1052-CNRS UMR5286, Université de Lyon, Centre Léon Bérard, 69008, Lyon, France., Richaud M; Apoptosis, Cancer and Development Laboratory- Equipe labellisée 'La Ligue', Labex DEVweCAN, Institut Convergence PLAsCAN, Centre de Cancérologie de Lyon, INSERM U1052-CNRS UMR5286, Université de Lyon, Centre Léon Bérard, 69008, Lyon, France., Laval PA; Apoptosis, Cancer and Development Laboratory- Equipe labellisée 'La Ligue', Labex DEVweCAN, Institut Convergence PLAsCAN, Centre de Cancérologie de Lyon, INSERM U1052-CNRS UMR5286, Université de Lyon, Centre Léon Bérard, 69008, Lyon, France., Rama N; Apoptosis, Cancer and Development Laboratory- Equipe labellisée 'La Ligue', Labex DEVweCAN, Institut Convergence PLAsCAN, Centre de Cancérologie de Lyon, INSERM U1052-CNRS UMR5286, Université de Lyon, Centre Léon Bérard, 69008, Lyon, France., Goldschneider D; Netris Pharma, Centre Léon Bérard, 69008, Lyon, France., Paradisi A; Apoptosis, Cancer and Development Laboratory- Equipe labellisée 'La Ligue', Labex DEVweCAN, Institut Convergence PLAsCAN, Centre de Cancérologie de Lyon, INSERM U1052-CNRS UMR5286, Université de Lyon, Centre Léon Bérard, 69008, Lyon, France., Gourdin N; Targeting of the Tumor and its Immune Environnement, Centre de Cancérologie de Lyon, INSERM U1052-CNRS UMR5286, Université de Lyon, Centre Léon Bérard, 69008, Lyon, France., Chabaud S; UBET, Centre Léon Bérard, Lyon, France., Treilleux I; UBET, Centre Léon Bérard, Lyon, France., Gadot N; Pathology Department, Centre Léon Bérard, Lyon, France., Ray-Coquard I; Pathology Department, Centre Léon Bérard, Lyon, France., Depil S; Netris Pharma, Centre Léon Bérard, 69008, Lyon, France., Decaudin D; Laboratory of Preclinical Investigations, Translational Research Department, Institut Curie, Université Paris-Sciences-et-Lettres, 75005, Paris, France., Némati F; Laboratory of Preclinical Investigations, Translational Research Department, Institut Curie, Université Paris-Sciences-et-Lettres, 75005, Paris, France., Marangoni E; Laboratory of Preclinical Investigations, Translational Research Department, Institut Curie, Université Paris-Sciences-et-Lettres, 75005, Paris, France., Mery-Lamarche E; Department of Pathology, IUCT Oncopole, Toulouse, France., Génestie C; Department of Pathology, Gustave Roussy, Villejuif, France., Tabone-Eglinger S; Pathology Department, Centre Léon Bérard, Lyon, France., Devouassoux-Shisheboran M; Department of Pathology, Hospices Civils de Lyon, 69002, Lyon, France., Moore KJ; Department of Medicine, Leon H. Charney Division of Cardiology, New York University School of Medicine, New York, NY, USA., Gibert B; Apoptosis, Cancer and Development Laboratory- Equipe labellisée 'La Ligue', Labex DEVweCAN, Institut Convergence PLAsCAN, Centre de Cancérologie de Lyon, INSERM U1052-CNRS UMR5286, Université de Lyon, Centre Léon Bérard, 69008, Lyon, France. benjamin.gibert@lyon.unicancer.fr., Mehlen P; Apoptosis, Cancer and Development Laboratory- Equipe labellisée 'La Ligue', Labex DEVweCAN, Institut Convergence PLAsCAN, Centre de Cancérologie de Lyon, INSERM U1052-CNRS UMR5286, Université de Lyon, Centre Léon Bérard, 69008, Lyon, France. patrick.mehlen@lyon.unicancer.fr.; Netris Pharma, Centre Léon Bérard, 69008, Lyon, France. patrick.mehlen@lyon.unicancer.fr., Bernet A; Apoptosis, Cancer and Development Laboratory- Equipe labellisée 'La Ligue', Labex DEVweCAN, Institut Convergence PLAsCAN, Centre de Cancérologie de Lyon, INSERM U1052-CNRS UMR5286, Université de Lyon, Centre Léon Bérard, 69008, Lyon, France. agnes.bernet@lyon.unicancer.fr.; Netris Pharma, Centre Léon Bérard, 69008, Lyon, France. agnes.bernet@lyon.unicancer.fr. |
المصدر: | Cell death and differentiation [Cell Death Differ] 2023 Oct; Vol. 30 (10), pp. 2201-2212. Date of Electronic Publication: 2023 Aug 26. |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Nature Publishing Group Country of Publication: England NLM ID: 9437445 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-5403 (Electronic) Linking ISSN: 13509047 NLM ISO Abbreviation: Cell Death Differ Subsets: MEDLINE |
أسماء مطبوعة: | Publication: <2003->: London : Nature Publishing Group Original Publication: London : Edward Arnold, c1994- |
مواضيع طبية MeSH: | Netrin-1*/metabolism , Neoplastic Stem Cells*/metabolism , Neoplastic Stem Cells*/drug effects , Neoplastic Stem Cells*/pathology , Myeloid-Derived Suppressor Cells*/metabolism , Myeloid-Derived Suppressor Cells*/drug effects , Drug Resistance, Neoplasm*/drug effects , Immune Checkpoint Inhibitors*/pharmacology , Immune Checkpoint Inhibitors*/therapeutic use, Animals ; Humans ; Mice ; Female ; Cell Line, Tumor ; Ovarian Neoplasms/drug therapy ; Ovarian Neoplasms/pathology ; Ovarian Neoplasms/metabolism ; Breast Neoplasms/drug therapy ; Breast Neoplasms/pathology ; Breast Neoplasms/metabolism |
مستخلص: | Drug resistance and cancer relapse represent significant therapeutic challenges after chemotherapy or immunotherapy, and a major limiting factor for long-term cancer survival. Netrin-1 was initially identified as a neuronal navigation cue but has more recently emerged as an interesting target for cancer therapy, which is currently clinically investigated. We show here that netrin-1 is an independent prognostic marker for clinical progression of breast and ovary cancers. Cancer stem cells (CSCs)/Tumor initiating cells (TICs) are hypothesized to be involved in clinical progression, tumor relapse and resistance. We found a significant correlation between netrin-1 expression and cancer stem cell (CSC) markers levels. We also show in different mice models of resistance to chemotherapies that netrin-1 interference using a therapeutic netrin-1 blocking antibody alleviates resistance to chemotherapy and triggers an efficient delay in tumor relapse and this effect is associated with CSCs loss. We also demonstrate that netrin-1 interference limits tumor resistance to immune checkpoint inhibitor and provide evidence linking this enhanced anti-tumor efficacy to a decreased recruitment of a subtype of myeloid-derived suppressor cells (MDSCs) called polymorphonuclear (PMN)-MDSCs. We have functionally demonstrated that these immune cells promote CSCs features and, consequently, resistance to anti-cancer treatments. Together, these data support the view of both a direct and indirect contribution of netrin-1 to cancer stemness and we propose that this may lead to therapeutic opportunities by combining conventional chemotherapies and immunotherapies with netrin-1 interfering drugs. (© 2023. The Author(s), under exclusive licence to ADMC Associazione Differenziamento e Morte Cellulare.) |
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معلومات مُعتمدة: | P01 HL131481 United States HL NHLBI NIH HHS |
المشرفين على المادة: | 158651-98-0 (Netrin-1) 0 (Immune Checkpoint Inhibitors) 0 (NTN1 protein, human) |
تواريخ الأحداث: | Date Created: 20230826 Date Completed: 20240430 Latest Revision: 20240430 |
رمز التحديث: | 20240501 |
مُعرف محوري في PubMed: | PMC10589209 |
DOI: | 10.1038/s41418-023-01209-x |
PMID: | 37633969 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1476-5403 |
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DOI: | 10.1038/s41418-023-01209-x |