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 contribution | Immunological aspects of anticancer chemotherapy |
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langue originale | Français |
Pages (de - à) | 1469-1489 |
Nombre de pages | 21 |
journal | Bulletin de l'Academie Nationale de Medecine |
Volume | 192 |
Numéro de publication | 7 |
Les DOIs | |
état | Publié - 1 janv. 2008 |
mots-clés
- Apoptosis
- Dendritic cells
- Drug therapy
- Immunity, natural