[Immunological aspects of anticancer chemotherapy].

Abstract

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 chemo/radiotherapy) 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-of-function 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.

• Authors: Laurence Zitvogel, Antoine Tesniere, Lionel Apetoh, François Ghiringhelli, Guido Kroemer
• Journal: Bulletin de l'Academie nationale de medecine (Bull Acad Natl Med) Vol. 192 Issue 7 Pg. 1469-87; discussion 1487-9 (Oct 2008) ISSN: 0001-4079 [Print] Netherlands
• Vernacular Title: Contribution du système immunitaire a l'efficacité des chimiothérapies anticancéreuses.
• PMID: 19445369 (Publication Type: English Abstract, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Neoplasm
• Antineoplastic Agents
• HMGB1 Protein
• Recombinant Fusion Proteins
• TLR4 protein, human
• Toll-Like Receptor 4

Topics

• Antigen Presentation
• Antigens, Neoplasm (immunology)
• Antineoplastic Agents (pharmacology, therapeutic use)
• Apoptosis (drug effects, immunology)
• Breast Neoplasms (drug therapy, genetics, immunology, mortality, radiotherapy, surgery)
• Cell Line, Tumor (drug effects, immunology)
• Combined Modality Therapy
• Dendritic Cells (immunology)
• Disease-Free Survival
• HMGB1 Protein (genetics, physiology)
• HeLa Cells (immunology)
• Humans
• Immunologic Surveillance (drug effects)
• Melanoma (pathology)
• Models, Immunological
• Neoplasms (drug therapy, immunology)
• Polymorphism, Single Nucleotide
• Radiotherapy (adverse effects)
• Recombinant Fusion Proteins (physiology)
• Retrospective Studies
• Toll-Like Receptor 4 (genetics, physiology)