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.