Lipid nanoparticle-mediated delivery of mRNA vaccine elicits HPV-specific CD8+ T cell expansion and promotes tumor regression

Single cell multi-omics profiling of CD8+ T cells revealed that intravenous vaccination induced two unique differentiation trajectories (IFN-response and exhaustion), among which CD8+ T cells undergoing IFN-response trajectory were enriched in the spleen while their counterparts undergoing exhaustion trajectory were enriched in the TME. Combination therapy with immune checkpoint blockades (anti-LAG3/anti-CTLA4) could further augment the expansion of HPV-specific CD8+ T cells, reinvigorate their proliferative capacity and also enhance the anti-tumor efficiency of intravenous vaccination. Our results showed that the mRNA vaccine-induced expansion of functional tumor-specific CD8+ T cells combined with immune checkpoint blockade is a promising approach for tumor immunotherapy.