TY - JOUR
T1 - mRNA-LNP vaccination orchestrates systemic immunity to control human papillomavirus-positive head and neck squamous cell carcinoma
AU - Qiu, Ke
AU - Mao, Minzi
AU - Song, Yao
AU - Duan, Xing
AU - Rao, Yufang
AU - Feng, Lan
AU - Cheng, Danni
AU - Shao, Xiuli
AU - Liang, Yanling
AU - Jiang, Chuanhuan
AU - Huang, Hai
AU - Li, Li
AU - Wang, Yan
AU - Li, Huifang
AU - Zhu, Mengli
AU - Wu, Sisi
AU - Xu, Wei
AU - Liu, Geoffrey
AU - Jablonska, Jadwiga
AU - Lang, Stephan
AU - Li, Shuaicheng
AU - Chen, Fei
AU - Peng, Xingchen
AU - Zheng, Yongbo
AU - Wang, Haiyang
AU - Liu, Jun
AU - Zhao, Yu
AU - Song, Xiangrong
AU - Ren, Jianjun
PY - 2025/12/9
Y1 - 2025/12/9
N2 - Messenger RNA (mRNA) vaccines have demonstrated significant potential in cancer immunotherapy by activating both innate and adaptive immunity. However, the detailed cellular and molecular dynamics underpinning these systemic immune responses remain incompletely understood. In this study, we characterized the systemic immune landscape following human papillomavirus (HPV)-targeted mRNA-lipid nanoparticle (LNP) vaccination using single-cell RNA sequencing (scRNA-seq) in a murine model of HPV-positive head and neck squamous cell carcinoma (HNSCC). Our study revealed a coordinated remodeling of the systemic immune landscape, involving the tumor microenvironment (TME), tumor-draining lymph nodes (TDLNs), spleen, and blood. Notably, we pioneered a distinct interferon-stimulated gene (ISG) signature across multiple lymphoid subsets in TDLNs, driven by the LNP component, which contributed to rapid, non-antigen-specific immune activation. Additionally, HPV mRNA-LNP vaccination induced an antigen-specific cycling burst of immune cells that mediated tumor control through a systemic coordination of multi-directional differentiation into anti-tumor cell compositions. These findings enhance our understanding of how mRNA-LNP vaccination orchestrates systemic anti-tumor responses and highlight the therapeutic potential of targeting ISG-expressing and cycling immune cells to improve vaccine efficacy, paving the way for future clinical applications in HPV-related cancers.
© 2025 The Authors.
AB - Messenger RNA (mRNA) vaccines have demonstrated significant potential in cancer immunotherapy by activating both innate and adaptive immunity. However, the detailed cellular and molecular dynamics underpinning these systemic immune responses remain incompletely understood. In this study, we characterized the systemic immune landscape following human papillomavirus (HPV)-targeted mRNA-lipid nanoparticle (LNP) vaccination using single-cell RNA sequencing (scRNA-seq) in a murine model of HPV-positive head and neck squamous cell carcinoma (HNSCC). Our study revealed a coordinated remodeling of the systemic immune landscape, involving the tumor microenvironment (TME), tumor-draining lymph nodes (TDLNs), spleen, and blood. Notably, we pioneered a distinct interferon-stimulated gene (ISG) signature across multiple lymphoid subsets in TDLNs, driven by the LNP component, which contributed to rapid, non-antigen-specific immune activation. Additionally, HPV mRNA-LNP vaccination induced an antigen-specific cycling burst of immune cells that mediated tumor control through a systemic coordination of multi-directional differentiation into anti-tumor cell compositions. These findings enhance our understanding of how mRNA-LNP vaccination orchestrates systemic anti-tumor responses and highlight the therapeutic potential of targeting ISG-expressing and cycling immune cells to improve vaccine efficacy, paving the way for future clinical applications in HPV-related cancers.
© 2025 The Authors.
UR - https://www.webofscience.com/wos/woscc/full-record/WOS:001634409400005
U2 - 10.1016/j.omtn.2025.102780
DO - 10.1016/j.omtn.2025.102780
M3 - RGC 21 - Publication in refereed journal
C2 - 41438364
SN - 2162-2531
VL - 36
JO - Molecular Therapy - Nucleic Acids
JF - Molecular Therapy - Nucleic Acids
IS - 4
M1 - 102780
ER -
SDG 3 Good Health and Well-being