Accéder directement au contenu Accéder directement à la navigation
Article dans une revue

TLR4/IFNγ pathways induce tumor regression via NOS II-dependent NO and ROS production in murine breast cancer models

Abstract : Toll-like receptor (TLR) 4 agonists have emerged as a new group of molecules used for cancer therapy. They have been exploited to enhance the immunogenicity of current chemotherapeutic regimens. However, their effects on cancer cells remain elusive. Here, we showed that a TLR4 agonist, namely a synthetic lipid A analog (ALA), OM-174, exhibits antitumor effects in several mammary tumor mouse models. We also showed that immune components are involved in such effects, as attested to by the failure of ALA to induce tumor regression or an increase of animal survival in mice knocked-out for interferon g (IFNg) or TLR4. TLR4 and IFNg receptor (INFR2) expressed by cancer cells are involved in the antitumor efficacy of ALA since this last did not inhibit tumor growth in mice bearing a tumor but lacking TLR4 or IFNg receptor 2 (IFNR2). Mechanistic investigations revealed that nitric oxide (NO), superoxide and peroxynitrite produced by uncoupling of inducible NO synthase (NOS II) in cancer cells are key mediators of ALA and IFNg-mediated tumor growth inhibition. We present here a comprehensive picture of tumor cell death induction, in vivo and in vitro, by immunotherapy and for the first time the involvement of the TLR4/IFNg/NOS II pathway in immunotherapy was investigated.
Type de document :
Article dans une revue
Liste complète des métadonnées

https://hal-univ-bourgogne.archives-ouvertes.fr/hal-03433384
Contributeur : Catherine Vergely Connectez-vous pour contacter le contributeur
Soumis le : mercredi 17 novembre 2021 - 17:02:46
Dernière modification le : vendredi 19 novembre 2021 - 11:09:22

Fichier

koni-05-05-1123369.pdf
Fichiers éditeurs autorisés sur une archive ouverte

Identifiants

Citation

Myriam Lamrani, Nejia Sassi, Catherine Paul, Nadhir Yousfi, Jean-Luc Boucher, et al.. TLR4/IFNγ pathways induce tumor regression via NOS II-dependent NO and ROS production in murine breast cancer models. OncoImmunology, Taylor & Francis, 2016, 5 (5), pp.e1123369. ⟨10.1080/2162402x.2015.1123369⟩. ⟨hal-03433384⟩

Partager

Métriques

Consultations de la notice

24

Téléchargements de fichiers

16