Cell-based immunotherapies hold great promise for the future treatment of cancer. Among the recent discoveries in cancer immunotherapy is the concept of immunogenic cell death (ICD). When tumor cell death is induced in an immunogenic way, dying tumor cells can be recognized and engulfed by dendritic cells (DCs), resulting in DC-activation and tumor antigen presentation. As such, dying tumor cells can become a cell-based vaccine. This project aims to investigate HIFU-induced cell death modalities to further maximize the ICD-inducing potential of high-intensity focused ultrasound (HIFU), a non-invasive and clinically relevant tumor ablation strategy that uses ultrasound waves to locally destroy tumor tissue. Following preliminary experiments, showing HIFU-induced ICD, we want to further tweak the HIFU-parameters to obtain an optimized protocol for immunogenic tumor treatment. In synergy with this, we aim to boost the induced immune responses by the local delivery of immune checkpoint inhibiting nanobodies by making use of clinically relevant mRNA nanomedicines that passively target inflammatory monocytes after systemic injection, which results in high mRNA expression rates at inflamed areas. As these immune cells are the major source of immune suppressive cell types in the tumor, they are ideal targets for tumor modulation, more specific for tackling adaptive resistance mechanisms.