Our results demonstrate that glioma-derived HMGB1 released from dying cells is necessary for the clonal expansion of CD8+ T cells specific for glioma antigens including the Trp2180–188 peptide (H-2Kb), and that the effects of HMGB1 are mediated through TLR2 signaling on tumor-infiltrating DCs. This evidence concerns the gene CD8A and central nervous system cancer.