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. 2023 Sep 29;8:144. doi: 10.1038/s41541-023-00733-8

Fig. 1. Schematic representation of the formation and immunological mechanism of HPV mRNA-LNPs.

Fig. 1

Active tumor targeting was achieved through both the activation of systemic innate immune responses and tumor-specific immune responses. Once entering the body, on one hand, HPV mRNA-LNPs were uptaken by dendritic cells in the spleen and stimulate a significant release of type I IFNs for the activation of systemic innate immune responses. On the other hand, HPV mRNA-LNPs were uptaken by dendritic cells in the tumor microenvironment and activate tumor-specific effector immune responses. Nevertheless, persistent antigen stimulation resulted in CD8+ T cell exhaustion, which is characterized by gradually increasing expression of multiple inhibitory receptor genes, providing a backdoor for the functional impairment of effector cells. Therefore, combination therapy of HPV mRNA-LNP vaccination with immune checkpoint blockade boosted effector CD8+ T cells while restoring their anti-tumor function, thus further promoting tumor regression.