Therapeutic strategies for interfering with coinhibitory molecules. First, blocking antibodies can be used to abrogate binding between coinhibitory molecules with the tumor-reactive T cell and tumor cells, thereby enhancing T-cell responses. In addition, DC therapy can be combined with antagonistic antibodies to boost the tumor-specific effect of DC vaccination. Another method to circumvent coinhibitory signaling during DC vaccination is silencing of coinhibitory molecules. Delivery of siRNA can be achieved either by electroporation or via lipid nanoparticles. Finally, coinhibitory molecules, which are differentially more involved in GVHD, can be stimulated by agonistic antibodies. This will attenuate GVHD-specific T-cell responses, thereby preventing attack of GVHD-prone tissues.