Ex vivo- and in vivo-induced dead tumor cells as modulators of antitumor responses.

Joint application of standard tumor therapies like radiotherapy and/or chemotherapy with immune therapy has long been considered not to fit. However, it has become accepted that immune responses may contribute to the elimination of cancer cells. We present how in vivo-induced tumor cell death by irradiation, chemotherapeutic agents, or hyperthermia can be rendered more immunogenic. High hydrostatic pressure is introduced as an innovative inactivation method for tumor cells used as vaccines. Annexin A5, being a natural occurring ligand for phosphatidylserine that is exposed by dying tumor cells, renders apoptotic tumor cells immunogenic and induces tumor regression. Combinations of irradiation with hyperthermia may also foster antitumor responses. For preparation of autologous tumor cell vaccines, high hydrostatic pressure is suitable to induce immunogenic cancer cell death. Future work will be aimed toward evaluating which combination and chronological sequence of radiotherapy, chemotherapy, hyperthermia, annexin A5, and/or autologous tumor cell vaccines will induce specific and long-lasting antitumor immunity.