mRNA-LNP vaccination-based immunotherapy augments CD8+ T cell responses against HPV-positive oropharyngeal cancer
Ke Qiu,
Xing Duan,
Minzi Mao,
Yao Song,
Yufang Rao,
Danni Cheng,
Lan Feng,
Xiuli Shao,
Chuanhuan Jiang,
Hai Huang,
Yan Wang,
Huifang Li,
Xuemei Chen,
Sisi Wu,
Dan Luo,
Fei Chen,
Xingchen Peng,
Yongbo Zheng,
Haiyang Wang,
Jun Liu,
Yu Zhao,
Xiangrong Song,
Jianjun Ren
Affiliations
Ke Qiu
Department of Otolaryngology-Head & Neck Surgery and Department of Critical Care Medicine, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University
Xing Duan
Department of Otolaryngology-Head & Neck Surgery and Department of Critical Care Medicine, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University
Minzi Mao
Department of Otolaryngology-Head & Neck Surgery and Department of Critical Care Medicine, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University
Yao Song
Department of Otolaryngology-Head & Neck Surgery and Department of Critical Care Medicine, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University
Yufang Rao
Department of Otolaryngology-Head & Neck Surgery and Department of Critical Care Medicine, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University
Danni Cheng
Department of Otolaryngology-Head & Neck Surgery and Department of Critical Care Medicine, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University
Lan Feng
Department of Otolaryngology-Head & Neck Surgery and Department of Critical Care Medicine, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University
Xiuli Shao
Department of Otolaryngology-Head & Neck Surgery and Department of Critical Care Medicine, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University
Chuanhuan Jiang
Department of Otolaryngology-Head & Neck Surgery and Department of Critical Care Medicine, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University
Hai Huang
Department of Otolaryngology-Head & Neck Surgery and Department of Critical Care Medicine, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University
Yan Wang
Research Core Facility of West China Hospital, Sichuan University
Huifang Li
Research Core Facility of West China Hospital, Sichuan University
Xuemei Chen
Research Core Facility of West China Hospital, Sichuan University
Sisi Wu
Research Core Facility of West China Hospital, Sichuan University
Dan Luo
Research Core Facility of West China Hospital, Sichuan University
Fei Chen
Department of Otolaryngology-Head & Neck Surgery and Department of Critical Care Medicine, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University
Xingchen Peng
Department of Biotherapy and National Clinical Research Center for Geriatrics, Cancer Center, West China Hospital, Sichuan University
Yongbo Zheng
Department of Otolaryngology-Head & Neck Surgery and Department of Critical Care Medicine, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University
Haiyang Wang
Department of Otolaryngology-Head & Neck Surgery and Department of Critical Care Medicine, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University
Jun Liu
Department of Otolaryngology-Head & Neck Surgery and Department of Critical Care Medicine, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University
Yu Zhao
Department of Otolaryngology-Head & Neck Surgery and Department of Critical Care Medicine, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University
Xiangrong Song
Department of Otolaryngology-Head & Neck Surgery and Department of Critical Care Medicine, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University
Jianjun Ren
Department of Otolaryngology-Head & Neck Surgery and Department of Critical Care Medicine, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University
Abstract Although mRNA vaccines are known as potent activators of antigen-specific immune responses against infectious diseases, limited understanding of how they drive the functional commitment of CD8+ T cells in tumor microenvironment (TME) and secondary lymphoid organs hinders their broader application in cancer immunotherapy. Here, we systematically evaluated the immunological effects of a lipid nanoparticle (LNP)-encapsulated mRNA vaccine that encodes human papillomavirus E7 protein (HPV mRNA-LNP), a tumor-specific antigen of HPV-positive oropharyngeal squamous cell carcinoma (OPSCC). HPV mRNA-LNP vaccination activated overall and HPV-specific CD8+ T cells, as well as differentially drove the functional commitment of CD8+ T cells through distinct IFN-response and exhaustion trajectories in the spleen and TME, respectively. Combination therapies of HPV mRNA-LNP vaccination with immune checkpoint blockades boosted HPV-specific CD8+ T cells while maintaining their anti-tumor function, thus further promoting tumor regression. Our results showed that the HPV mRNA-LNP vaccination combined with immune checkpoint blockade is a promising approach for immunotherapy of HPV-positive OPSCC.
