Adjuvant role for cell death during chemo- and radiotherapy of cancer?

Evaluation of: Apetoh L, Ghiringhelli F, Tesniere A et al. Toll-like receptor 4-dependent contribution of the immune system to anti-cancer chemotherapy and radiotherapy. Nat. Med. 13, 1050-1059 (2007). Chemotherapy and radiotherapy are supposed to mediate their anticancer activity via the direct elimination of tumor cells. Dying cells, however, also release molecules that promote the activation and the functional maturation of the most potent antigen-presenting cells, the dendritic cells. Mature dendritic cells are endowed with the ability to cross-prime T cells against the antigens contained in the dead cells. This paper evaluates the results from a recent article in which the success of some protocols for anticancer therapy depends, besides their direct cytotoxic effect, on the induction of a specific immune response: the effect is mediated both in mice and humans through the release by dying tumor cells of the nuclear protein high-mobility group 1 protein and by its interaction with Toll-like receptor 4. Larger studies on various therapeutic regimens are needed to evaluate the general relevance of this observation.