Immunotherapy with immune checkpoint blockade (ICB) has shown limited benefits in hepatocellular carcinoma (HCC) and other cancers, mediated in part by the immunosuppressive tumor microenvironment (TME). This study examines the effects of restoring p53 expression on the immune TME and ICB efficacy using a CXCR4-targeted mRNA nanoparticle platform. Combining this platform with anti-PD-1 therapy effectively reprograms the immune TME, leading to improved antitumor effects compared to either treatment alone. This demonstrates the reversal of immunosuppression in HCC by p53 mRNA nanomedicine combined with ICB.

Yuling Xiao, Jiang Chen, Hui Zhou, Xiaodong Zeng, Zhiping Ruan, Zhangya Pu, Xingya Jiang, Aya Matsui, Lingling Zhu, Zohreh Amoozgar, Dean Shuailin Chen, Xiangfei Han, Dan G. Duda, Jinjun Shi