HMGB1 mediates endogenous TLR2 activation and brain tumor regression.

ABSTRACT:

Background

Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor that carries a 5-y survival rate of 5%. Attempts at eliciting a clinically relevant anti-GBM immune response in brain tumor patients have met with limited success, which is due to brain immune privilege, tumor immune evasion, and a paucity of dendritic cells (DCs) within the central nervous system. Herein we uncovered a novel pathway for the activation of an effective anti-GBM immune response mediated by high-mobility-group box 1 (HMGB1), an alarmin protein released from dying tumor cells, which acts as an endogenous ligand for Toll-like receptor 2 (TLR2) signaling on bone marrow-derived GBM-infiltrating DCs.

Methods and findings

Using a combined immunotherapy/conditional cytotoxic approach t

SUBMITTER: Curtin JF 

PROVIDER: S-EPMC2621261 | biostudies-literature | 2009 Jan

REPOSITORIES: biostudies-literature