METHOD FOR EFFECTING LOCALIZED, NON-SYSTEMIC AND SYSTEMIC, IMMUNOGENIC TREATMENT OF CANCER USING ERP57 TRANSLOCATION

摘要

Anthrocyclines-treated tumor cells are particularly effective in eliciting an anti-cancer immune response, where the rDNA-damaging agents, such as etoposide and mitomycin C do not induce immunogenic cell death. Anthracyclines induce the rapid, pre-apoptotic translocation of ERP57 to the cell surface. Knock down of ERP57 inhibit the translocation of CRT, suppressed the phagocytosis of anthracyclines-treated tumor cells by dendritic cells and abolished their immunogenicity in mammals, such as mice. In contrast, the blockade of ERP57 with blocking antibody had no effect on phagocytosis of anthracyclines-treated tumor cells by dendritic cells and their immunogenicity in mammals, such as mice. The anthracyclines-induced ERP57 translocation was mimicked by inhibition of the protein phosphatase1/GADD34 complex. Administration of recombinant ERP57 did not restore the immunogenicity of cell death elicited by etoposide and mitomycin C, or enhanced their antitumor effects in vivo, in contrast to the administration of recombinant CRT. These data identify the presence of ERP57 crucial for the translocation of CRT and to induce immunogenic cell death which will activate a anti-cancer immune responses.