High hydrostatic pressure induces immunogenic cell death in human tumor cells
Recent studies have identified molecular events characteristic of immunogenic cell death, including surface exposure of calreticulin (CRT), the heat shock proteins HSP70 and HSP90, the release of high mobility group box protein 1 (HMGB1) and release of ATP from dying cells. We investigated the potential of high hydrostatic pressure (HHP) to induce immunogenic cell death in human tumor cells. HHP induced the rapid expression of HSP70, HSP90 and CRT on the cell surface. HHP also induced the release of HMGB1 and ATP. The interaction of dendritic cells (DCs) with HHP-treated tumor cells led to a more rapid rate of DC phagocytosis, upregulation of CD83, CD86 and HLA-DR and the release of IL-6, IL-12p70 and TNFα. DCs pulsed with tumor cells killed by HHP induced high numbers of tumor-specific T cells. DCs pulsed with HHP-treated tumor cells also induced the lowest number of regulatory T cells (Tregs). In addition, we found that key features of the endoplasmic reticulum (ER) stress-mediated apoptotic pathway, such as reactive oxygen species production, phosphorylation of the translation initiation factor eIF2α and activation of caspase 8, were activated by HHP treatment. Therefore, HHP acts as a reliable and potent inducer of immunogenic cell death in human tumor cells. © 2014 Wiley Periodicals, Inc.