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The interaction between HMGB1 and TLR4 dictates the outcome of anticancer chemotherapy and radiotherapy
Author(s) -
Apetoh Lionel,
Ghiringhelli François,
Tesniere Antoine,
Criollo Alfredo,
Ortiz Carla,
Lidereau Rosette,
Mariette Christophe,
Chaput Nathalie,
Mira JeanPaul,
Delaloge Suzette,
André Fabrice,
Tursz Thomas,
Kroemer Guido,
Zitvogel Laurence
Publication year - 2007
Publication title -
immunological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.839
H-Index - 223
eISSN - 1600-065X
pISSN - 0105-2896
DOI - 10.1111/j.1600-065x.2007.00573.x
Subject(s) - immunogenic cell death , cytotoxic t cell , cancer research , biology , hmgb1 , immunology , radiation therapy , cancer , metastasis , immune system , chemotherapy , immunotherapy , medicine , in vitro , biochemistry , genetics , inflammation
Summary: For the last four decades, the treatment of cancer has relied on four treatment modalities, namely surgery, radiotherapy, cytotoxic chemotherapy, and hormonotherapy. Most of these therapies are believed to directly attack and eradicate tumor cells. The emerging concept that cancer is not just a disease of a tissue or an organ but also a host disease relies on evidence of tumor‐induced immunosuppression and polymorphisms in genes involved in host protection against tumors. This theory is now gaining new impetus, based on our recent data showing that optimal therapeutic effects require the immunoadjuvant effect of tumor cell death induced by cytotoxic anticancer agents. Here, we show that the release of the high mobility group box 1 protein (HMGB1) by dying tumor cells is mandatory to license host dendritic cells (DCs) to process and present tumor antigens. HMGB1 interacts with Toll‐like receptor 4 (TLR4) on DCs, which are selectively involved in the cross‐priming of anti‐tumor T lymphocytes in vivo . A TLR4 polymorphism that affects the binding of HMGB1 to TLR4 predicts early relapse after anthracycline‐based chemotherapy in breast cancer patients. This knowledge may be clinically exploited to predict the immunogenicity and hence the efficacy of chemotherapeutic regimens.