Fiche publication
Date publication
mai 2016
Journal
Oncoimmunology
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BETTAIEB Ali
,
Pr PAUL Catherine
,
Pr VERGELY Catherine
Tous les auteurs :
Lamrani M, Sassi N, Paul C, Yousfi N, Boucher JL, Gauthier N, Labbé J, Seignez C, Racoeur C, Athias A, Guerreiro R, Vergely C, Rochette L, Bettaieb A, Jeannin JF
Lien Pubmed
Résumé
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 γ (IFNγ) or TLR4. TLR4 and IFNγ 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 IFNγ 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 IFNγ-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/IFNγ/NOS II pathway in immunotherapy was investigated.
Référence
Oncoimmunology. 2016 May;5(5):e1123369
