Academic Journal
New soluble CSF-1R-dimeric mutein with enhanced trapping of both CSF-1 and IL-34 reduces suppressive tumor-associated macrophages in pleural mesothelioma
| Τίτλος: | New soluble CSF-1R-dimeric mutein with enhanced trapping of both CSF-1 and IL-34 reduces suppressive tumor-associated macrophages in pleural mesothelioma |
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| Συγγραφείς: | Joalland, Noémie, Quéméner, Agnès, Deshayes, Sophie, Humeau, Romain, Maillasson, Mike, Lebihan, Héloïse, Salama, Apolline, Fresquet, Judith, Remy, Séverine, Mortier, Erwan, Blanquart, Christophe, Guillonneau, Carole, Anegon, Ignacio |
| Συνεισφορές: | Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology (U1064 Inserm - CR2TI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ), Team 2 : Cell and gene engineering in tolerance, fertility and regenerative medicine (Team 2 - U1064 Inserm - CR2TI), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers (CRCI2NA), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Manipulation of Lymphocytes for Immunotherapy (CRCI2NA / Eq 12), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Immunomodulation of the Tumor Microenvironment and Immunotherapy of Thoracic Cancers (CRCI2NA / Eq 1), BioCore Nantes, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes)-Nantes Université (Nantes Univ), ANR-11-LABX-0016,IGO,Immunothérapies Grand Ouest(2011) |
| Πηγή: | ISSN: 2051-1426 ; Journal for Immunotherapy of Cancer ; https://inserm.hal.science/inserm-05036353 ; Journal for Immunotherapy of Cancer, 2025, 13 (3), pp.e010112. ⟨10.1136/jitc-2024-010112⟩. |
| Στοιχεία εκδότη: | CCSD BMJ Publishing Group |
| Έτος έκδοσης: | 2025 |
| Συλλογή: | Université de Nantes: HAL-UNIV-NANTES |
| Θεματικοί όροι: | Cytokine, Immunotherapy, Macrophages, Mesothelioma, Tolerance, [SDV]Life Sciences [q-bio] |
| Περιγραφή: | International audience ; Background: Colony stimulating factor-1 receptor (CSF-1R) and its ligands CSF-1 and interleukin (IL)-34 have tumorigenic effects through both induction of suppressive macrophages, and survival/proliferation of tumor cells. In addition, the IL-34 tumorigenic effect can also be mediated by its other receptors, protein-tyrosine phosphatase zeta, Syndecan-1 (CD138) and triggering receptor expressed on myeloid cells 2. Small tyrosine kinase inhibitors are used to block CSF-1R signaling but lack specificity. Neutralizing anti-CSF-1 and/or IL-34 antibodies have been proposed, but their effects are limited. Thus, there is a need for a more specific and yet integrative approach.Methods: A human mutated form of the extracellular portion of CSF-1R was in silico modelized to trap both IL-34 and CSF-1 with higher affinity than the wild-type CSF-1R by replacing the methionine residue at position 149 with a Lysine (M149K). The extracellular portion of the mutated CSF-1R M149K was dimerized using the immunoglobulin Fc sequence of a silenced human IgG1 (sCSF-1RM149K-Fc). Signaling through CSF-1R, survival of monocytes and differentiation of suppressive macrophages were analyzed using pleural mesothelioma patient's samples and mesothelioma/macrophage spheroids in vitro and in vivo in the presence of sCSF-1RM149K-Fc or sCSF-1R-Fc wild type control (sCSF-1RWT-Fc).Results: We defined that the D1 to D5 domains of the extracellular portion of CSF-1R were required for efficient binding to IL-34 and CSF-1. The mutein sCSF-1RM149K-Fc trapped with higher affinity than sCSF-1RWT-Fc both CSF-1 and IL-34 added in culture and naturally produced in mesothelioma pleural effusions. sCSF-1RM149K-Fc inhibited CSF-1R signaling, survival and differentiation of human suppressive macrophage in vitro and in vivo induced by pleural mesothelioma cells. Neutralization of IL-34 and CSF-1 by sCSF-1RM149K-Fc also resulted in higher killing of pleural mesothelioma cells by a tumor-specific CD8+ T cell clone in mesothelioma/macrophage ... |
| Τύπος εγγράφου: | article in journal/newspaper |
| Γλώσσα: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/40101804; PUBMED: 40101804; PUBMEDCENTRAL: PMC11927444 |
| DOI: | 10.1136/jitc-2024-010112 |
| Διαθεσιμότητα: | https://inserm.hal.science/inserm-05036353 https://inserm.hal.science/inserm-05036353v1/document https://inserm.hal.science/inserm-05036353v1/file/e010112.full%20copie.pdf https://doi.org/10.1136/jitc-2024-010112 |
| Rights: | http://creativecommons.org/licenses/by/ ; info:eu-repo/semantics/OpenAccess |
| Αριθμός Καταχώρησης: | edsbas.47AC775C |
| Βάση Δεδομένων: | BASE |
| DOI: | 10.1136/jitc-2024-010112 |
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