Supplementary Figure 1 from A Prime-Boost Vaccination Approach Induces Lung Resident Memory CD8+ T Cells Derived from Central Memory T Cells That Prevent Tumor Lung Metastasis
posted on 2024-10-01, 07:40authored byHaoran Xu, Ming Yue, Runhong Zhou, Pui Wang, Michael Yik-Chun Wong, Jinlin Wang, Huarong Huang, Bohao Chen, Yufei Mo, Rachel Chun-Yee Tam, Biao Zhou, Zhenglong Du, Haode Huang, Li Liu, Zhiwu Tan, Kwok-Yung Yuen, Youqiang Song, Honglin Chen, Zhiwei Chen
Gag mosaic expressing LAIV vaccine construction and characterization
Funding
Research Grants Council Theme-Based Research Scheme
Collaborative Research Fund
Research Grant Council General Research Fund
The University Development Fund and Li Ka Shing Faculty of Medicine Matching Fund
Health@InnoHK (Center for Viology, Vaccionology and Therapeutics)
Innovation and Technology Commission (ITC)
University Grants Committee (UGC) -The Hong Kong Theme-Based Research Scheme
Emergency Key Program of Guangzhou Laboratory
Wellcome Trust
Donations from the Friends of Hope Education Fund
History
ARTICLE ABSTRACT
Memory T cells play a key role in immune protection against cancer. Vaccine-induced tissue-resident memory T (TRM) cells in the lung have been shown to protect against lung metastasis. Identifying the source of lung TRM cells can help to improve strategies, preventing tumor metastasis. Here, we found that a prime-boost vaccination approach using intramuscular DNA vaccine priming, followed by intranasal live-attenuated influenza-vectored vaccine (LAIV) boosting induced higher frequencies of lung CD8+ TRM cells compared with other vaccination regimens. Vaccine-induced lung CD8+ TRM cells, but not circulating memory T cells, conferred significant protection against metastatic melanoma and mesothelioma. Central memory T (TCM) cells induced by the DNA vaccination were major precursors of lung TRM cells established after the intranasal LAIV boost. Single-cell RNA sequencing analysis indicated that transcriptional reprogramming of TCM cells for differentiation into TRM cells in the lungs started as early as day 2 post the LAIV boost. Intranasal LAIV altered the mucosal microenvironment to recruit TCM cells via CXCR3-dependent chemotaxis and induced CD8+ TRM-associated transcriptional programs. These results identified TCM cells as the source of vaccine-induced CD8+ TRM cells that protect against lung metastasis.Significance: Prime-boost vaccination shapes the mucosal microenvironment and reprograms central memory T cells to generate lung resident memory T cells that protect against lung metastasis, providing insights for the optimization of vaccine strategies.