TUMOR IMMUNOGENICITY IS DETERMINED BY THE MECHANISM OF CELL-DEATH VIAINDUCTION OF HEAT-SHOCK-PROTEIN EXPRESSION

In situ killing of tumor cells using suicide gene transfer to generate death by a non-apoptotic pathway was associated with high immunogenic ity and induction of heat shock protein (hsp) expression. In contrast, a syngeneic colorectal tumor line, CMT93, killed predominantly by apo ptosis, showed low levels of hsp expression and less immunogenicity. W hen apoptosis was inhibited in CMT93 cells by overexpression of bcl-2, hsp was also induced. Furthermore, when cDNA encoding hsp70 was stabl y transfected into B16 and CMT93 cells, its expression significantly e nhanced the immunogenicity of both tumors. Increased levels of hsp, in duced by non-apoptotic cell killing, may provide an immunostimulatory signal in vivo which helps break tolerance to tumor antigens. These fi ndings have important implications for the development of novel anti-c ancer therapies aimed at promoting patients' immune responses to their own tumors.