mRNA-LNP vaccination-based immunotherapy augments CD8+ T cell responses against HPV-positive oropharyngeal cancer

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 i...

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Bibliographic Details
Published in:npj vaccines 2023-09, Vol.8 (1), p.144-144, Article 144
Main Authors: Qiu, Ke, Duan, Xing, Mao, Minzi, Song, Yao, Rao, Yufang, Cheng, Danni, Feng, Lan, Shao, Xiuli, Jiang, Chuanhuan, Huang, Hai, Wang, Yan, Li, Huifang, Chen, Xuemei, Wu, Sisi, Luo, Dan, Chen, Fei, Peng, Xingchen, Zheng, Yongbo, Wang, Haiyang, Liu, Jun, Zhao, Yu, Song, Xiangrong, Ren, Jianjun
Format: Article
Language:English
Subjects:
631/250/590/2293
631/67/1059/2325
Antigens
Biomedical and Life Sciences
Biomedicine
Human papillomavirus
Immunization
Immunotherapy
Infectious Diseases
Lymphocytes
Medical Microbiology
Public Health
Throat cancer
Tumors
Vaccine
Vaccines
Virology
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Summary: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.
ISSN:2059-0105
2059-0105
DOI:10.1038/s41541-023-00733-8