Resumen
Current immunotherapies based on blockade of immunosuppressive elements provide limited results in liver cancer patients. Here we tested whether combination of this therapy with a vaccine based on the Cold-Inducible RNA Binding Protein (CIRP) would improve its efficacy. Combination of immunotherapy with a CIRP-based vaccine increased vaccine immunogenicity and, when tested in several mouse models of liver cancer, resulted in better therapeutic effects. Despite good immune responses observed in peripheral organs, lymphocytes infiltrating the tumor appeared exhausted, with a weak functional capacity. Finally, by using the same strategy, we prepared a new CIRP-based vaccine containing glypican-3, human antigen commonly found in patients with liver cancer. An equivalent combination enclosing this new vaccine was also highly immunogenic. This suggests that CIRP-based vaccines may enhance the beneficial effects provided by current immunotherapies. However, they should also consider incorporating new elements to overcome limitations observed in tumor lymphocytes.