Contribution du système immunitaire à l'efficacité des chimiothérapies anticancéreuses

Laurence Zitvogel, Antoine Tesniere, Lionel Apetoh, François Ghiringhelli, Guido Kroemer

    Résultats de recherche: Contribution à un journalArticleRevue par des pairs

    39 Citations (Scopus)

    Résumé

    For over 40 years, four therapeutic modalities, namely surgery, radiotherapy, chemotherapy and hormone therapy have formed the core of anticancer treatments. Their mode of action is thought to involve a direct cytotoxic action on tumor cells. Recently, the discovery of tumor-associated immunosuppression and tumor immunosurveillance has led to cancer being reconsidered not only as an organ disease but also as a host disease. This new concept is supported by the recent discovery of the immunogenic effects of tumor cell death induced by a variety of cytotoxic drugs. This work describes a new pathway of tumor-derived antigen presentation mediated by the alarmin HMGB1 (released by dying tumor cells in response to chemolradiotherapy) and by TLR4 on dendritic cells. In this model, TLR4 recognizes ? tumor-derived antigens, leading to T cell activation and to the induction of an antitumor immune response. Accordingly, we show that breast cancer patients bearing a loss-offunction mutation of the TLR4 receptor have shorter disease-free survival, confirming the major role of the immune system in the response to cytotoxic treatments. The response to chemotherapy and/or radiotherapy may thus combine both direct cytotoxic effects and the development of long-term antitumor immunity. We anticipate that these new results will have major impact on cancer management.

    Titre traduit de la contributionImmunological aspects of anticancer chemotherapy
    langue originaleFrançais
    Pages (de - à)1469-1489
    Nombre de pages21
    journalBulletin de l'Academie Nationale de Medecine
    Volume192
    Numéro de publication7
    Les DOIs
    étatPublié - 1 janv. 2008

    mots-clés

    • Apoptosis
    • Dendritic cells
    • Drug therapy
    • Immunity, natural

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