Primary tumor tissue lysates are enriched in heat shock proteins and induce the maturation of human dendritic cells

Upon exposure to lysates or supernatants of necrotic transformed cell lines , human dendritic cells (DCs) undergo maturation. In contrast, DCs exposed to apoptotic transformed cell lines or necrotic lysates of primary cells re main immature. Analysis of supernatants of necrotic transformed cell lines showed them to be enriched in the heat shock proteins (hsp)70 and gp96, in contrast to supernatants of primary cells. Likewise, cells from a variety o f primary human tumors contained considerably higher levels of lisp than th eir normal autologous tissue counterparts. Of the majority of human tumors enriched in lisps (hsp70 and/or gp96), their corresponding lysates matured DCs. The maturation effect of tumor cell lysates was abrogated by treatment with boiling, proteinase K, and geldanamycin, an inhibitor of hsps, sugges ting that hsps rather than endotoxin or DNA were the responsible factors. S upporting this idea, highly purified, endotoxin-depleted hsp70, induced DC maturation similar to that seen with standard maturation stimuli LPS and mo nocyte conditioned medium. These results suggest that the maturation activi ty inherent within tumor cells and lines is mediated at least in part by hs ps. The release of hsps in vivo as a result of cell injury should promote i mmunity through the maturation of resident DCs.