Development of effective immunotherapy by combining interventions on key points in the anti-tumor immune network

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In this sturdy, we have attempted to develop effective cancer immunotherapy by combining immune-regulating interventions on multiple important points in the cancer related positive and negative immune responses. We have developed and evaluated the following interventions; 1) interventions to induce immunogenic cancer cell death, 2) cancer antigens expressed in cancer stem cells which are resistant to chemotherapy, 3) interventions to stimulate antigen presenting dendritic cells for anti-cancer T-cell activation, 4) interventions to activate anti-cancer T-cells, 5) interventions to reverse cancer-induced immunosuppression. Using mouse tumor models, we have evaluated cancer immunotherapies in which the above interventions are appropriately combined, particularly with immune-checkpoint blockade therapies. These results may lead to development of more effective cancer immunotherapies through evaluation in the future clinical trials.