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Curr Opin Immunol. 2008 Oct;20(5):518-23. doi: 10.1016/j.coi.2008.04.012. Epub 2008 Jul 1.

HMGB1: a two-headed signal regulating tumor progression and immunity.

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  • 1Laboratory of Clinical Immunology, San Raffaele Scientific Institute, DIBIT 3A1, Via Olgettina 58, 20132 Milano, Italy.


Cells of the innate immune system sense tissue damage recognizing in the extracellular environment bona fide intracellular moieties, like high mobility group box 1 (HMGB1). In the case of tumors, HMGB1 recognition has a paradoxical dual effect: it promotes tumor neoangiogenesis and triggers protective anti-neoplastic T-cell responses. Recent advances in the study of HMGB1 have identified candidate molecular mechanisms underlying these apparently contrasting outcomes. A surprising role for innate receptors, including toll like receptor 4 (TLR4), in the response to conventional cancer radio and chemotherapy has also recently emerged, providing new insight into the mechanisms by which these treatments actually work.

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