A TLR4 Agonist Induces Osteosarcoma Regression by Inducing an Antitumor Immune Response and Reprogramming M2 Macrophages to M1 Macrophages - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Cancers Année : 2023

A TLR4 Agonist Induces Osteosarcoma Regression by Inducing an Antitumor Immune Response and Reprogramming M2 Macrophages to M1 Macrophages

Paul Berchard
  • Fonction : Auteur
  • PersonId : 1331833
Lhorra Abbes
  • Fonction : Auteur
  • PersonId : 1331834
Alexey Novikov
  • Fonction : Auteur
Marie Karanian
  • Fonction : Auteur
  • PersonId : 1077684
Jerome Kerzerho
Martine Caroff
  • Fonction : Auteur

Résumé

Osteosarcoma (OsA) has limited treatment options and stagnant 5-year survival rates. Its immune microenvironment is characterized by a predominance of tumor-associated macrophages (TAMs), whose role in OsA progression remain unclear. Nevertheless, immunotherapies aiming to modulate macrophages activation and polarization could be of interest for OsA treatment. In this study, the antitumor effect of a liposome-encapsulated chemically detoxified lipopolysaccharide (Lipo-MP-LPS) was evaluated as a therapeutic approach for OsA. Lipo-MP-LPS is a toll-like receptor 4 (TLR4) agonist sufficiently safe and soluble to be IV administered at effective doses. Lipo-MP-LPS exhibited a significant antitumor response, with tumor regression in 50% of treated animals and delayed tumor progression in the remaining 50%. The agent inhibited tumor growth by 75%, surpassing the efficacy of other immunotherapies tested in OsA. Lipo-MP-LPS modulated OsA’s immune microenvironment by favoring the transition of M2 macrophages to M1 phenotype, creating a proinflammatory milieu and facilitating T-cell recruitment and antitumor immune response. Overall, the study demonstrates the potent antitumor effect of Lipo-MP-LPS as monotherapy in an OsA immunocompetent model. Reprogramming macrophages and altering the immune microenvironment likely contribute to the observed tumor control. These findings support the concept of immunomodulatory approaches for the treatment of highly resistant tumors like OsA.
Fichier principal
Vignette du fichier
cancers-15-04635.pdf (14.92 Mo) Télécharger le fichier
Origine Fichiers éditeurs autorisés sur une archive ouverte

Dates et versions

hal-04374321 , version 1 (05-01-2024)

Identifiants

Citer

Iseulys Richert, Paul Berchard, Lhorra Abbes, Alexey Novikov, Kamel Chettab, et al.. A TLR4 Agonist Induces Osteosarcoma Regression by Inducing an Antitumor Immune Response and Reprogramming M2 Macrophages to M1 Macrophages. Cancers, 2023, 15 (18), pp.4635. ⟨10.3390/cancers15184635⟩. ⟨hal-04374321⟩
23 Consultations
4 Téléchargements

Altmetric

Partager

Gmail Mastodon Facebook X LinkedIn More